Neoplasms

All Conditions

Rare Diseases

Rhabdomyosarcoma

Myosarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Sarcoma

Soft Tissue Sarcoma

Rhabdomyosarcoma (RMS) stands for the most frequent soft tissue sarcoma in children and, adolescents and young adults (AYA, 15-25-year-old population), accounting for approximately half of the whole soft tissue sarcomas in these populations.. Conversely, RMS represents a very small proportion of the soft tissue sarcomas in adults (3%), that is less than 1% of all solid cancers of adults.

To date, previous studies undertaken among the paediatric population have pointed out several prognostic factors such as tumor localisation, tumor invasiveness at diagnosis, tumor size, histological subset, and treatment plans. Age at diagnosis remains an independent prognostic factor.

RMS management is consensual in Europe for paediatric population, essentially based on the protocol RMS 2005 within the framework of the European Paediatric Soft tissue sarcoma Study Group (EpSSG). Care in AYAs remain heterogeneous and are either achieved in paediatric department, according to EpSSG guidelines, or in oncology department, known as "adult unit", depending on ESMO (European Society for Medical Oncology), which are non-specific recommendations for the management of rhabdomyosarcoma.

No consensus has been published yet for RMS in AYA despite the growing interest in cancers in AYA population - topic.supported by the French National Cancer Institute (INCa) - and the increasing network between paediatricians and adult-oncologists. Thus management of RMS in AYA remains patchy/unequal depending on the type of care unit.

Herein, with the support of the Oscar Lambret Center, we aim at assessing and identifying clinico-biological prognostic factors of rhabdomyosarcoma in AYA. Eventually, we hope to offer a standardized treatment to this population. Data collected from medical file will be anonymised in a confidential database of which the recipient is the sponsor of the study.

The ancillary study will aim at characterizing the molecular profile of the difficult-to-classify RMS subtypes (fusiform or pleomorphic subsets) in molecular biology for ambiguous cases.

From a scientific point of view, this study aims at understanding the parameters that may influence the prognosis of RMS in AYAs by evaluating various clinical and biological factors.

Biologically, molecular profiling of RMS in AYA may improve the characterization of this tumour in this age group.

At the clinical level, the completeness of the data collected will lead to a better description of RMS in AYAs. We hope to harmonize their therapeutic management by providing therapeutic adjustments according to population subsets.

Finally, these results could also help to adapt the therapeutic management of AYAs within the framework of the European protocol that is currently under construction, and will involve both children and adults.

Rhabdomyosarcoma (RMS) is a rare tumor, with an incidence rate estimated at 4.5-6.9/1,000,000 in paediatric and, adolescent and young adult (AYA, 15 -25 years old) populations. RMS stands for the most frequent soft tissue sarcoma in children and adolescents, accounting for approximately half of the whole soft tissue sarcomas in these populations. Conversely, RMS represents a very small proportion of the soft tissue sarcomas in adults (3%), that is less than 1% of the solid cancers of the adult. To date, previous studies undertaken among the paediatric population have pointed out several prognostic factors such as tumor localisation, tumor invasiveness at diagnosis, tumor size, histological subset, and treatment plans. Age at diagnosis remains an independent prognostic factor. MYOD1 gene expression profile, more common in AYA, also seems to impair the prognosis.

RMS management is consensual in Europe for paediatric population, essentially based on the protocol RMS 2005 within the framework of the European Paediatric Soft tissue sarcoma Study Group (EpSSG). Care in AYAs remain heterogeneous and are either achieved in paediatric department, according to EpSSG guidelines, or in oncology department, known as "adult unit", depending on ESMO (European Society for Medical Oncology), which are non-specific recommendations for the management of rhabdomyosarcoma.

No consensus has been published yet for RMS in AYA despite the growing interest in cancers in AYA population - topic.supported by the French National Cancer Institute (INCa) - and the increasing network between paediatricians and adult-oncologists. Thus management of RMS in AYA remains patchy/unequal depending on the type of care unit.

Principal study

* To evaluate the prognostic value in terms of Progression Free Survival (PFS), in AYA patients with RMS, of clinical factors known as prognostic in children, and of biological factors (MYOD1 mutation in non-alveolar tumor; FOXO1).
* To describe clinical, histological and biological characteristics of RMS in AYA.
* To describe the therapeutic strategy according to the type of department (pediatric, AYA or adults):
* To evaluate the impact on PFS of treatment strategy
* To estimate the Overall Survival (OS) in AYA with RMS
* To estimate the OS curve after relapse for patients who achieved complete remission during first line of treatment

Exploratory study Molecular profiling of RMS with the following subtypes: with fusiform cells (Embryonal RMS with fusiform cells vs adult RMS with fusiform cells or sclerosing) or pleomorphic (Embryonal RMS with anaplasia vs adult pleomorphic RMS) by RNAseq, and by CGH for ambiguous cases.

Methodology Clinical data from the different databases will be merged using a standardized format.

A pathology review of the slides is planned as well as a molecular characterization in borderline cases and unusual subtypes. MYOD1 mutations and molecular profile will be investigated for embryonal RMS.

Patient and treatment characteristics will be described with median, range, mean and standard deviation for continuous variables and in terms of frequency and percent of each modality for categorical variables.

PFS will be estimated using Kaplan-Meier method from diagnosis until relapse, progression or death from any cause. Patients alive without progression will be censored at the date of last news.

OS will be estimated using Kaplan-Meier method from diagnosis until death from any cause.

OS after relapse will be estimated using Kaplan-Meier method from the date of first relapse until the death whatever the cause. Patients alive will be censored at the date of last news.

Prognostic factors of PFS will be analyzed using Cox models after check of the proportional hazard assumption. The following factors will be evaluated:

* age: continuous or 15-18 vs 18-25
* tumor size: ≤ 5cm vs \> 5cm
* primary tumor site according to the EPSSG classification: favorable (orbit, head and non parameningeal neck, paratesticular, vagina, uterus) vs unfavorable (head and parameningeal, vesico -prostatic, limb, other)
* IRS stage for primary tumor
* nodal and metastatic involvement at diagnostic
* histology (alveolar vs embryonic vs pleomorphic vs other)
* PAX3-FOXO1 and PAX7-FOXO1 fusion gene status, MYOD1 mutation The impact of treatment intervention on PFS will be evaluated using a Cox model stratified or adjusted over prognostic factors identified at the previous step.

Tissue extracted at diagnosis from biopsy or from surgical resection of the primary tumor

Clinico-biological Study/Characterization of Rhabdomyosarcoma in Adolescents and Young Adults, 15-25-year-old Patients

Clinico-biological Study/Characterization of Rhabdomyosarcoma in AYA (Adolescents and Young Adults, 15-25-year-old Patients)

To estimate progression-free survival in AYA patients with RMS, according to clinical factors known as prognostic in children, and of biological factors (MYOD1 mutation in non-alveolar tumor; FOXO1).

Clinical data from the different databases will be merged using a standardized format in order to describe the Clinical parameters of RMS in AYA

Description of the RMS in AYA using biological characteristics (FOXO1, MYOD1 - where appropriate -, CGH-array profile)

Description of the therapeutic strategy according to the different type of patients (paediatric, AYA, or adult):

OS will be defined as the time from diagnosis to death or last contact with the patient.

Centre Leon Berard

Société Française de lutte contre les Cancers et les leucémies de l'Enfant et l'adolescent

French Sarcoma Group

Ligue contre le cancer, France

Centre Oscar Lambret

Heart and Blood Diseases

Symptoms and General Pathology

Substance Related Disorders

Wounds and Injuries

Heart Failure

Cardiotoxicity

Heart Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Central Nervous System Depressants

All Drugs and Chemicals

Other Dietary Supplements

Benzocaine

Tannic Acid

CORE consists of exercise therapy, CVD risk factor management, and behavioural support for 3 months.

Exercise therapy: Staff will prescribe and deliver a standardized, yet individually tailored (based on CPET results), aerobic exercise programs consisting of two days of supervised, facility- and home-based high-intensity interval training (HIIT) and one day of supervised home-based moderate-intensity continuous training (MICT) per week. Exercise HRs and durations will be monitored using an accurate commercially available wrist-worn HR monitor and PA tracker.

CVD risk factor management: CVD risk factors will be assessed and treated according to Canadian guidelines.

Behavioural support: All participants will receive a planned sequence of educational and instructional material via email and ongoing PAYA-CS tailored education and peer support during the follow-up period using a peer support online system.

The Support group will receive the behavioural support only. The timing and nature of all education, information provided to Support participants will be identical to what is provided to CORE participants. All Support participants will receive the same wrist-worn HR monitor and PA tracker as the CORE participants and will be given the challenge of meeting and maintaining the updated PA guidelines for cancer survivors (i.e., 90 to 150 minutes of moderate to vigorous intensity PA per week).

Exercise therapy, CVD risk factor management for the first 6 months (as per current standards in CR models) and behavioural support for the entire 2-year intervention period

Cardio-oncology Rehabilitation (CORE)

Behavioural support via professionals and peer support and recommended physical activity guidelines for cancer survivors, to encourage physical activity.

Support

Cardiovascular disease (CVD) is a major contributor to morbidity and mortality in pediatric, adolescent and young adult (AYA) cancer survivors (hereafter referred to as PAYA-CS). Exercise is a cornerstone of CVD prevention and treatment; yet, exercise has not been adopted as a standard of care in PAYA-CS at high CVD risk. The HIMALAYAS trial is designed to evaluate the feasibility and preliminary impact of an exercise-based CR on cardiovascular (CV) and psychosocial health, as well as CVD risk, in PAYA-CS with mild heart dysfunction (stage B heart failure (SBHF)). The primary objective of the HIMALAYAS pilot study is to assess the feasibility of a two-phase randomized controlled trial designed to evaluate impact of a 'CR-like' cardio-oncology rehabilitation (CORE) intervention on CV, psychosocial, and behavioural outcomes at 6 and 24 months, compared to behavioural support only (Support) in PAYA-CS. Screened PAYA-CS without SBHF and those with SBHF who do not participate in the RCT will be enrolled in a passive behavioural support (Support) group. The primary outcome is study feasibility, defined according to three primary criteria (i.e., participant recruitment, safety, and adherence). Secondary outcomes include additional feasibility metrics (e.g., intervention safety and tolerability) and exploratory efficacy outcomes including peak cardiorespiratory fitness (VO2peak), cardiac function (e.g., global longitudinal strain (GLS)), CVD risk factor control (e.g. insulin resistance), and patient-reported outcomes (e.g. anxiety). Our central hypothesis is that the conduct of a larger RCT comparing the impact of CORE versus non-intervention control will be feasible indicated by the achievement of our primary feasibility criteria. Our exploratory hypothesis is that we will generate preliminary evidence that CORE can improve VO2peak, cardiac function, CVD risk factor, and patient-reported outcomes over 6- and 24-month timepoints, relative to control.

Over 90,000 North Americans are diagnosed with cancer before the age of 40. Improved cancer therapies have led to an exponential growth in the number of pediatric, adolescent, and young adult cancer survivors (PAYA-CS) who are expected to live 50-60 years beyond diagnosis. However, PAYA-CS are at increased risk of developing multiple cancer- and treatment-related morbidities including poor fitness (e.g., low VO2peak), hypertension (HTN), diabetes, and poor mental health, which all contribute to premature cardiovascular disease (CVD). The prevalence of CVD events (e.g. heart failure, heart attack, stroke) is up to 23.8% in adult survivors of pediatric cancers with long term follow-up after treatment. The incidence of subclinical CVD, which is a precursor to CVD events, is even higher in PAYA-CS; up to 40%, 11%, and 5% experience subclinical cardiomyopathy measured by abnormal global longitudinal strain (GLS), diastolic dysfunction (DD) or mild reduction in left ventricular ejection fraction (LVEF), respectively, and 18% experience reduced aerobic fitness. The treatment of modifiable CVD risk factors must be considered a fundamental target for improving CVD health-related outcomes in PAYA-CS. To this end, exercise and best-practices for CVD risk factor modification are integral to a cardiac rehabilitation (CR) model. Traditional cardiac rehabilitation models for patients with CVD (consisting of exercise, CVD risk factor treatment, and patient education) are safe and effective in improving HRQoL, morbidity, and mortality risk. However, by virtue of their age and low short-term CVD risk, PAYA-CS do not meet traditional criteria for initiating CR and are less likely to receive treatments to reduce CVD risk.

PAYA-CS with stage B heart failure (SB¬HF): (1) are at high risk for subsequent HF/CVD death; (2) have lower cardiopulmonary fitness; and (3) are more likely to benefit from CVD risk factor management. Considering that PAYA-CS have an estimated 33% prevalence of SBHF, this vulnerable cohort of cancer survivors represent an opportunity for intervention that is highly feasible and potentially impactful. Exercise is a preferred method for optimizing health and survival in PAYA-CS. However, we need models that safely and effectively deliver exercise interventions that meet the unique needs of this population. The cardio-oncology rehabilitation (CORE) model is an intervention that would provide PAYA-CS with SBHF a supervised and home-based exercise therapy, CVD risk factor modification, and behavioural support to reduce the risk of CVD. Nevertheless, due to the ambitious nature of the study, it is vital that we conduct a pilot version of the study to determine the feasibility and needed changes to achieve the best possible results.

The primary objective of the HIMALAYAS pilot study is to assess the feasibility, safety, and tolerability of a (1) two-arm RCT-based comparison of the CORE and Support interventions in PAYA-CS with SBHF, and (2) parallel passive behavioural support (PBS) cohort of PAYA-CS at high-risk of cancer-related CVD. The exploratory objectives of the study include (1) to compare the changes in primary exploratory outcome (VO2peak) and secondary exploratory outcomes (markers of cardiac function, CVD risk factor management, and patient-reported outcomes) between a CORE and Support intervention for PAYA-CS from baseline (T0) to 6-month (T1) follow-up and (2) to compare the changes in the primary and secondary exploratory outcomes between (1) CORE and Support from T0 to 12-month (T2) and 24-month (T3) follow-up, and (2) CORE, Support, and PBS from T0 to T3.

Cardio-oncology Rehabilitation (CORE) Group: CORE consists of exercise therapy, CVD risk factor management for the first 6 months (as per current standards in CR models) and behavioural support for the entire 2-year intervention period.

Support Group: The Support group will receive the behavioural support only. The timing and nature of all education, information, and peer support provided to Support participants will be identical to what is provided to CORE participants. The key difference in the long-term behavioural support strategy between CORE and Support participants is how weekly exercise goals are defined. Unlike the CORE participants who will be encouraged to use the personal activity intelligence (PAI) Score, Support participants will be given the challenge of meeting and maintaining the updated physical activity (PA) guidelines for cancer survivors (i.e., 90 to 150 minutes of moderate to vigorous-intensity PA per week).

Passive Behavioural Support (PBS) Groups: All PBS cohort participants will receive the same wrist-worn heart rate monitor and PA tracker as the CORE and Support participants. However, PBS participants will be blindly randomized to one of two passive behavioural support interventions (PBS1 and PBS2). PBS1 participants will be asked to download the same PAI Health application as CORE participants and will similarly be given the challenge of meeting and maintaining a weekly PAI Score ≥100 throughout the 18-month follow-up period. PBS2 participants will be asked to download and use the Map My Walk (Under Armour, Baltimore) application and will be challenged to meet and maintain the updated PA guidelines for cancer survivors (i.e., 90 to 150 minutes of moderate to vigorous intensity PA per week).

The Harmonized Interventions to Maintain Health Via Appropriate Risk Factor Modification and Lifestyle Changes in Pediatric, Adolescent and Young Adult Cancer Survivors Pilot Study

Measured with an average of 3 readings (after discarding an initial test reading) by an automated measurement device as per the Hypertension Canada guidelines.

Measured with an average of 2 readings taken via ECG during the resting period during the cardiac screening procedures.

Measured through fasting cholesterol profile and Apo B levels

Measured through whole-body insulin sensitivity (Matsuda index)

Measured through hepatic insulin sensitivity (HOMA-IR)

Measured through pancreatic beta-cell function (ISSI-2).

Measured through Godin Leisure Time PA Questionnaire (GLTPAQ). Score of \>24 = active, score of 14-23 = moderately active, score of \<14 = insufficiently active

Measured through wrist-worn heart rate with physical activity monitor

Measured using the Social Support Survey-Clinical (SSS-C) form, a 5-item survey designed to measure five dimensions of social support (listening, task challenge, emotional reality confirmation, and tangible assistance); higher score = more social support

Measured using the Multidimensional Self-Efficacy for Exercise Scale (MSES) to measure three behavioural subdomains: task, scheduling, and coping; Scale 0-90, higher score indicates higher self-efficacy for exercise.

Measured using the National Health and Nutrition Examination Survey (NHANES) Food Frequency Questionnaire (FFQ), a 139-item, semi-quantitative inventory to assess the potential influence of dietary changes on primary and secondary outcomes.

Measured using self-reported measures to determine the potential influence of changes in smoking habits on primary and secondary outcomes.

Measured using the Generalized Anxiety Disorder (GAD-7), a 7-item inventory that assesses 2-week anxiety symptom frequency on a 0-3 scale, with higher scores reflecting higher symptom frequency. A cut-off of ≥10 indicates some degree of clinical anxiety

Measured using the Patient Health Questionnaire (PHQ-9), a 9-item inventory that assesses 2-week depressive symptom frequency on a 0-3 scale, with higher scores reflecting higher symptom frequency. The PHQ-9 has been validated in cancer survivors using a cut-off of ≥8 to indicate some degree of clinical depression.

Measured using the Medical Outcomes Survey Short-Form, (SF-12).

Measured using the Working Alliance Inventory Short-Revised (WAI-SR) form. Increased score indicates therapeutic alliance.

Defined as the percent of consenting patients based on the total number of otherwise eligible participants (OEP; patients meeting all eligibility criteria) approached

Defined as the number and frequency of testing- and intervention-related serious adverse events (SAEs) according to the Common Terminology Criteria for Adverse Events

Defined as relative dose intensity as the percent of total dose of exercise performed relative to the total planned dose prescribed and quantified according to metabolic equivalents

Defined as the average number of OEP identified each month

Defined as the percent of consenting patients who successfully complete baseline assessments based on the total number of consenting patients

Defined as the number and frequency of testing- and intervention-related non-serious adverse events

Defined as the percent completion of all cardiopulmonary exercise tests (CPETs) tests at baseline (T0) and primary follow-up (T1)

Defined as the percent of all tests which are adapted for functional or safety reasons

Defined as the percent of all exercise sessions which are adapted for functional or safety reasons

Defined as the percent of patients who discontinue intervention participation prior to the planned end of the intervention period

Defined as the percent of patients who miss =\>3 consecutive sessions within the intervention period

Defined as the percent of exercise sessions requiring a dose reduction during training (i.e., intensity or duration) relative to the total number of sessions completed. Total number of exercise sessions with a reduction in intensity or a reduction in duration will be combined into the numerator when calculating the percentage of affected sessions.

Defined as the percent of exercise sessions requiring unplanned early termination

Defined as the percent of sessions which required pre-exercise modification of the target exercise intensity due to a pre-exercise screening indication (e.g., fatigue, pain)

Defined as the percent of exercise sessions completed based on the total number of sessions prescribed.

Defined as the percent of pharmaceutical doses taken based on the total number of doses prescribed (applicable only to those that are provided pharmaceutical therapy for CVD risk factor modification.

Defined as the percent of behavioural support resources accessed, based on the number of doses prescribed

defined as the average number of participants achieving their weekly PA goals of meeting and maintaining either a PAI-Score of ≥100 or weekly cancer exercise guidelines (i.e., 90 to 150 minutes of moderate to vigorous intensity PA per week).

Defined as the percent loss to follow-up (not completing follow-up assessments)

University Health Network, Toronto

Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Communicable Diseases

Acquired Immunodeficiency Syndrome

HIV Infections

Immunologic Deficiency Syndromes

Virus Diseases

Papilloma

Syndrome

Blood-Borne Infections

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Lentivirus Infections

Retroviridae Infections

RNA Virus Infections

Slow Virus Diseases

Genital Diseases

Urogenital Diseases

Neoplasms, Squamous Cell

Neoplasms, Glandular and Epithelial

Vaccines

.5 mL dose injected IM at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0

.5 mL dose injected IM at 0, 2 and 6 months

Gardasil

Administration of online risk behavior and knowledge survey done at week 0.

Survey

Hoyoung M Maeng, M.D.

Background:

* Human papilloma virus (HPV) is a common sexually transmitted disease. There are more than 100 different HPV types, and both males and females can get HPV infection. Most people do not have any symptoms when they become infected and are able to get rid of the infection on their own. However, they can still become re-infected with the same or a different HPV type, and in some people HPV infection persists.
* Persistent HPV infection is associated with the development of precancerous lesions and cancer. HPV types are classified as either high risk or low risk based on whether their persistence will lead to cancer.
* Patients who have suppressed immune systems are at a higher risk for HPV-related complications. They are more likely to contract multiple HPV types and have more persistent infection that can lead to precancerous lesions or cancer, which are then difficult to treat and often recur.
* A recently approved vaccine for HPV induces immunity to HPV 6, 11, 16, and 18. It was shown to be highly effective in preventing infection with these HPV types, and is approved for use in females 9 to 26 years of age. However, much less is known about the vaccine s ability to induce immunity in males or individuals with suppressed immune systems.

Objectives:

- To investigate whether the HPV vaccine is safe to give and able to induce immunity in both female and male adolescents and young adults with HIV infection compared to healthy, HIV-negative persons of the same age.

Eligibility:

- Males and females, 12 to 26 years of age, divided into three groups: (1) Healthy and HIV-negative, (2) HIV-positive and on antiretroviral therapy, and (3) HIV-positive and not on antiretroviral therapy.

Design:

* Before beginning vaccination, participants will have a complete physical examination and blood drawn for routine blood tests, special tests of the immune system, antibody tests, and an HIV test.
* HPV vaccine will be given by injection into the muscle at 0, 2, and 6 months, according to the standard vaccination schedule.
* Patients with HIV infection will be monitored for a week following the first injection to test the level of HIV in the blood 3 days and 5 days after the first injection.
* Participants will also be asked to fill out a 10- to 15-minute Web-based survey about awareness, health behaviors, and personal choices related to risk factors for HIV, HPV, and other sexually transmitted diseases. Participants are not required to fill out the survey to receive the vaccine.
* The total duration of the study is 4 years. During the first year of the study, participants will return for six additional 1-day visits at months 1, 2, 3, 6, 7, and 12. Participants will return for 1-day visits every 6 months for the remaining 3 years.

Background:

Human papilloma virus (HPV) is one of the most common sexually transmitted diseases and a significant cause of cutaneous genital warts and anogenital cancer.

Infection with high-risk, oncogenic HPV types, most commonly types 16 and 18, is associated with low and high-grade cervical cellular abnormalities that are precursors to invasive cervical cancer, as well as vulvar and anal cancer, while HPV types 6 and 11 are associated with genital warts.

Persistence of HPV infection is more common in individuals with or at risk for chronic immunosuppression and HIV-infected individuals have a higher prevalence of HPV infection and HPV-associated anogential disease compared to age-matched HIV-negative controls.

Study Objectives:

To assess the safety and immunogenicity of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in HIV-infected preadolescents, adolescents and young adults 12-26 years of age.

To determine whether there are differences in HPV vaccine immunogenicity between HIV-infected and HIV negative age-matched controls.

To determine whether there are differences in HPV vaccine immunogenicity between HIV-infected patients receiving highly active antiretroviral therapy (HAART) and those not receiving HAART with similar CD4 and viral load parameters at entry.

To determine whether HPV vaccination alters HIV-1 RNA levels.

To investigate the impact of CD4 count and HIV-1 RNA levels on HPV vaccine immunogenicity.

To characterize HPV DNA positivity in the study cohort populations through oral/buccal and anogenital sampling at baseline.

To characterize HPV and HIV knowledge and risk and sexual behaviors in the study cohort populations.

Eligibility:

Individual Cohorts

Cohort 1: HIV-positive, CD4 cell count greater than or equal to 350 cells/mm3, HIV-1 RNA level by RT PCR less than or equal to 20,000 copies/ml, on stable HAART regimen for greater than or equal to 6 months.

Cohort 2: HIV-infected, CD4 cell count greater than or equal to 500 cells/mm3, HIV-1 RNA level by RT PCR less than or equal to 20,000 copies/ml, on no antiretroviral treatment.

Cohort 3: healthy, HIV-negative controls All Cohorts

Females and males age 12 to 26 years

Patients must have a hemoglobin greater than or equal to 10.0 gm/dL, neutrophil count (ANC) greater than or equal to 1500/mm3, platelet count greater than or equal to 75,000/mm3 and PT or PTT less than or equal to 1.5x ULN (with the exception of patients with known clotting disorders or lupus anticoagulant); SGPT/SGOT \< 2/5x ULN, total bilirubin less than or equal to 1.5x ULN unless attributable to protease inhibitor therapy.

Patients must test negative for hepatitis B virus and hepatitis C virus, unless the result is consistent with prior vaccination or prior infection with full recovery.

No use of investigational agents within 4 weeks of study enrollment or use of immunosuppressive or immunomodulating agents within 8 weeks of study entry.

Study Design:

This is a non-randomized, prospective, phase I study of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine.

The study includes 3 cohorts of pre-adolescents, adolescents and young adults 12-26 years of age as outlined under Eligibility Criteria. Each cohort will enroll 35 patients.

All study subjects will receive three doses of HPV vaccine at 0, 2 and 6 months administered IM.

Study participants will be monitored at months 0, 1, 2, 3, 6, 7, and 12 (+/- 2 weeks for each visit, and every 6 months (+/- 30 days) thereafter for 48 months total.

A Phase I Study of Quadrivalent Human Papilloma Virus (HPV) (Types 6, 11, 16, 18) Recombinant Vaccine in HIV-Infected and HIV-Negative Pre-Adolescents, Adolescents, and Young Adults

A Phase I Study of Quadrivalent Human Papilloma Virus (HPV) (Types 6, 11, 16, 18) Recombinant Vaccine in HIV-Infected and HIV-Negative Pre-Adolescents, Adolescents and Young Adults

Assessment of adverse events, their characteristics, duration and quantity for the entire study population.

National Cancer Institute (NCI)

Participants in the CORE group will have

1. A personalized, supervised exercise program ((in-person at intuition and virtual/ homebased exercises)
2. CV risk factor management,
3. behavioural support for the first 6 months. The behavioural support will continue for CORE participants from months 7-24. Behavioural support includes professionally guided and peer-enhanced exercise behavioural support based on behaviour change stage theories.

CORE participants will be provided a wrist-worn heart and physical activity monitor to use throughout the 24-month observation period.

Participants in the CON group will receive standard medical care and physical activity will be monitored by a wrist-worn activity tracker for 2 years.

Paaladinesh Thavendiranathan, MD

Krishna Mohan Chirra CRC

Krishna Mohan CRC

Pediatric, adolescent and young adult cancer survivors (PAYA-CS) are at higher risk of cardiovascular (CV) morbidity and mortality. This is a consequence of prior cancer-related therapies that have the potential of producing cardiac dysfunction, reducing cardiorespiratory fitness (reduced VO2peak) and psychosocial morbidities (i.e., anxiety and depression). A reduction of physical activity levels can evoke functional limitations resulting in a vicious cycle of reduced exercise tolerance and physical deterioration. To date, there is limited evidence on the use of non-pharmacological strategies such as Cardio-Oncology Rehabilitation (CORE) including structured exercise, behavioural support and risk factor management to improve the outcomes of this underserved population. The HIMALAYAS study is a randomized controlled trial designed to evaluate the impact of a CORE intervention (consisting of six-months home and onsite-based structured moderate to high-intensity aerobic exercise training and CVD risk factor management) on CV and psychosocial health, and the cardiovascular disease risk in PAYA-CS with mild heart dysfunction (stage B heart failure) compared to standard of care (i.e. providing guidance on the current exercise recommendations for cancer survivors). The primary objective of the HIMALAYAS study is to determine whether a six-month supervised CORE intervention, consisting of individualized moderate to high-intensity aerobic exercise training, CVD risk factor modification and enhanced online behavioral support, improves cardiorespiratory fitness (VO2peak; primary outcome), cardiac function, CVD risk factors and biomarkers, and patient-reported outcomes (PROs) at six- months follow-up compared to standard of care (CON) in PAYA-CS with stage B heart failure. The secondary objective is to assess the same outcomes at 12- and 24-months follow-up. We will recruit 336 patients across 5 sites in Canada and upto 134 patients at UHN in 3 years and conclude in 6 years.

Over 90,000 North Americans are diagnosed with cancer before the age of 40. Improved cancer therapies have led to an exponential growth in the number of pediatric, adolescent, and young adult cancer survivors (AYA-CS) who are expected to live 50-60 years beyond diagnosis. However, AYA-CS are at increased risk of developing multiple cancer- and treatment-related morbidities including poor fitness (e.g., low VO2peak), hypertension (HTN), diabetes, and poor mental health, which all contribute to premature cardiovascular disease (CVD). The prevalence of CVD events (e.g. heart failure, heart attack, stroke) is up to 23.8% in adult survivors of pediatric cancers with long term follow-up after treatment. The incidence of subclinical CVD, which is a precursor to CVD events, is even higher in AYA-CS; up to 40%, 11%, and 5% experience subclinical cardiomyopathy measured by abnormal global longitudinal strain (GLS), diastolic dysfunction (DD) or mild reduction in left ventricular ejection fraction (LVEF), respectively, and 18% experience reduced aerobic fitness. The treatment of modifiable CVD risk factors must be considered a fundamental target for improving CVD health-related outcomes in AYA-CS. To this end, exercise and best-practices for CVD risk factor modification are integral to a cardiac rehabilitation model. Traditional cardiac rehabilitation models for patients with CVD (consisting of exercise, CVD risk factor treatment, and patient education) are safe and effective in improving HRQoL, morbidity, and mortality risk. However, by virtue of their age and low short-term CVD risk, AYA-CS do not meet traditional criteria for initiating cardiac rehabilitation (CR) and are less likely to receive treatments to reduce CVD risk. AYA-CS with stage B heart failure (SBHF): (1) are at high risk for subsequent HF/CVD death; (2) have lower cardiopulmonary fitness; and (3) are more likely to benefit from CVD risk factor management. Considering that AYA-CS have an estimated 33% prevalence of SBHF, this vulnerable cohort of cancer survivors represent an opportunity for intervention that is highly feasible and potentially impactful. Exercise is a preferred method for optimizing health and survival in PAYA-CS. However, we need models that safely and effectively deliver exercise interventions that meet the unique needs of this population. The cardio-oncology rehabilitation (CORE) model is an intervention that would provide AYA-CS with SBHF a supervised and home-based high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) exercise therapy, CVD risk factor modification, and behavioural support to reduce the risk of CVD. The primary objective of the HIMALAYAS study is to determine whether supervised CORE (Group 1A) improves cardiorespiratory fitness (VO2peak; primary outcome), cardiac function, CVD risk factors and biomarkers, and PROs at 6 months (primary timepoint) as well as 12 and 24 months compared to standard of care group control group (CON) in AYA-CS with SBHF.

The secondary objective of the study is to assess the ongoing behavioural support strategy based on the exercise guidelines for cancer survivors (i.e. 90 to 150 minutes of moderate to vigorous PA per week) on VO2peak, cardiac function, CVD risk factors and biomarkers, and PROs at 24 months compared to standard of care \[CON\] in AYA-CS with SBHF. Due to the COVID-19 pandemic, CORE intervention will involve a facility-based HIIT session and home-based HIIT session (described as "HIIT at Home") per week.

The HIMALAYAS Trial and Lifestyle Changes in Pediatric, Adolescent and Young Adult Cancer Survivors Study: A Multicentre Randomized Controlled Trial

The Harmonized Interventions to Maintain Health Via Appropriate Risk Factor Modification and Lifestyle Changes in Pediatric, Adolescent and Young Adult Cancer Survivors Study: A Multicentre Randomized Controlled Trial

Measured using the Working Alliance Inventory Short-Revised (WAI-SR) form.

Defined as the percent of tests that achieve 'peak' termination criteria relative to the total number of tests completed across all time points

Defined as the number and frequency of testing-, intervention-, and non-intervention-related serious (i.e. Grade 3 to 5; NCI-CTCAE criteria) and non-serious (i.e. Grade 1 to 2; NCI-CTCAE criteria)

This variable applies only to CORE participants. Exercise adherence is defined as the relative dose intensity (i.e. the percent of total dose of exercise performed, relative to the total dose prescribed) and quantified according to metabolic equivalents.

Defined as the percent of pharmaceutical doses taken based on the total number of doses prescribed (applicable only to those that are provided pharmaceutical therapy for CVD risk factor modification)

Defined as the percent of behavioural support resources accessed, based on the number recommended (one per month)

Quantified as timepoint measures of oxygen utilization assessed via portable metabolic measurement system within the final 30 seconds of the warm-up, work and recovery periods, and the cool down during pre-specified high-intensity interval training sessions

Quantified as power output (watts) assessed cycle ergometer within the final 30 seconds of the warm-up, work and recovery periods, and the cool down during pre-specified high-intensity interval training sessions

Quantified via heart rate monitor or single-lead ECG within the final 30 seconds of the warm-up, work and recovery periods, and the cool down during pre-specified high-intensity interval training sessions

Quantified as total metabolic equivalent of task following HIIT sessions

Assessed via rating of perceived exertion scale (6-20) within the final 30 seconds of the warm-up, work and recovery periods, and the cool down during pre-specified high-intensity interval training sessions

Affective arousal is evaluated via the felt arousal scale that assesses energy/arousal level on a scale of 1 (low arousal) to 6 (high arousal) within the final 30 seconds of the warm-up, work and recovery periods, and the cool down during pre-specified HIIT sessions

The feeling scale is used to assess affective valence (pleasure/displeasure; feeling good/bad) on a scale of -5 (vey bad) to +5 (very good) within the final 30 seconds of the warm-up, work and recovery periods, and the cool down during pre-specified high-intensity interval training sessions

Measured using the Brief Relilience Scale (BRS), a 6-item inventory that assesses recovery, resistance, adaptation, and thriving.

Measured using two items based on the Canadian Community Health Survey assessing the average daily stress experienced that day and over the past week.

Assessed via ecological momentary assessments using brief reports completed 6 times a day on intervention weeks 1, 7, 16, 22, four weeks post intervention, and 26 weeks post intervention

Assessed via cardiopulmonary exercise test and quantified as VO2peak

Estimated using the V-slope method and according to the following criteria: i) an exaggerated response in the volume of carbon-dioxide (i.e., VCO2) relative to the volume of oxygen (i.e., VO2), and ii) the first identifiable break-point in in the minute ventilation (i.e., VE/VO2 vs work rate relationship).

Estimated according to the three-criterion discrimination technique: i) an excess VCO2 response relative to the VO2 response identified per the modified V-slope criteria; ii) the VE/VO2 to VO2 relationship having been flat or decreasing begins to increase without returning to baseline; and iii) there is no reciprocal decrease in PETCO2 at the point where PETO2 starts to rise systematically.

One-minute HR recovery (HRR; an index of post-exercise parasympathetic reactivation) will be calculated as the HR-difference between peak exercise and following one minute of quiet standing on the treadmill immediately post-test.

Assessed via tissue Doppler imaging (TDI)

Calculated using the average of the TDI septal and lateral annular velocities (e')

Assessed via Devereux formula and quantified as LV mass/body surface area: \>95 g/m2 for women or \>115 g/m2 for men

Assessed as \>0.42 relative wall thickness

Calculated as average of 3 readings measured via automated sphygmomanometer per the Hypertension Canada guidelines.

Assessed via homeostasis model assessment insulin resistance (HOMA-IR)

Assessed via the insulin secretion-sensitivity index-2 (ISSI-2)

Calculated as body weight (kg) divided by height (m) squared

Objectively assessed via wrist-worn physical activity/heart rate monitor to measure the intensity and duration of all planned and unplanned exercise during the study period

Subjectively assessed via Godin Leisure Time Physical Activity Questionnaire and reported as moderate-to-vigorous intensity physical activity (MVPA)

Measured using the Social Support Survey-Clinical (SSS-C) form, a 5-item survey designed to measure five dimensions of social support + a single item to assess cancer-specific social support.

Measured using the Multidimensional Self-Efficacy for Exercise Scale (MSES) to measure three behavioural subdomains: task, scheduling, and coping

Measured using the Generalized Anxiety Disorder (GAD-7), a 7-item inventory that assesses 2-week anxiety symptom frequency on a 0-3 scale, with higher scores reflecting higher symptom frequency. A cut-off of ≥10 indicates some degree of clinical anxiety.

Measured using the Medical Outcomes Survey Short-Form (SF-12).

Measured using the Health Service Utilization Inventory.

Centre hospitalier de l'Université de Montréal (CHUM)

Queen Elizabeth II Health Sciences Centre

Alberta Health services

Vancouver General Hospital

Université de Montréal

Dalhousie University

University of Alberta

University of British Columbia

University of Toronto

Skin and Connective Tissue Diseases

Osteosarcoma

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Facility and home-based multimodal prehabilitation (aerobic exercise training, resistance exercise training, nutrition support, stress management and mindfulness training)

Multimodal Prehabilitation

* Aerobic exercise

  * Home-based, high-intensity interval training (HIIT), 2 days/week
  * Home-based, moderate-intensity continuous training (MICT), 2-3 days/week
* Resistance exercise

  * Home-based, moderate-intensity resistance training, 2-3 d/wk, all major muscle groups (working around tumour-related deficits), 8-10 exercises, 12-15 repetitions, resistance bands and body weight based
* Nutrition

  * Protein intake 1.2-1.5 g/kg body weight/day in compliance with European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines
* Stress management

  * Daily mindfulness practice, 20 min/session, guided by audio file created at Mount Sinai Hospital

Multimodal prehabilitation

Daniel R Santa Mina, PhD

The purpose of this study was to evaluate the feasibility of a multimodal prehabilitation intervention intended to optimize postoperative recovery in adolescents and young adults (AYAs) diagnosed with soft tissue and bone-based sarcomas of the upper and lower extremities (extremity sarcomas; ES).

Objectives:

This objective of this study was to investigate the feasibility of multimodal prehabilitation for adolescents and young adults (AYAs) diagnosed with soft tissue and bone-based sarcomas of the upper and lower extremities (extremity sarcomas; ES) and explore its effects on measurements of health-related quality of life, physical function, length of hospital stays, and post-operative complications. Specific aims of the study included:

* To determine the feasibility of conducting a larger phase II investigation of HIIT-based multimodal prehabilitation according to three primary criteria, including (i) recruiting \>=50% of otherwise eligible patients (OEP; i.e., patients meeting all eligibility criteria), (ii) no patient experiences a testing-related or an intervention-related serious adverse event (SAE), and (iii) patients achieve an exercise intervention adherence rate of \>=70%.
* To further determine the feasibility of conducting a larger phase II investigation of HIIT-based multimodal prehabilitation according to the secondary feasibility criteria.
* To explore the preliminary effects of prehabilitation on measures of short-term perioperative outcomes including health-related quality of life, physical function, length of hospital stays, and post-operative complications.

Methods:

A single-arm, proof-of-concept trial design was informed by the ORBIT model of behavioural treatment development. Mixed methods were employed to obtain relevant context for investigating the feasibility of multimodal prehabilitation in newly diagnosed AYAs with ES within the circumstances of the COVID-19 pandemic.

Participants underwent virtual multimodal prehabilitation before undergoing major extremity sarcoma surgery. This program encompassed personalized exercise, nutrition, and stress management support delivered by a registered kinesiologist, registered dietitian, and clinical psychologist, respectively. The interventions were designed to enhance physical and psychological resilience to stress, with the objective of improving recovery outcomes and mitigating the risk of adverse events.

Feasibility (e.g., recruitment, safety, tolerability), physical function, and patient-reported outcomes were measured at baseline (T0), immediately preoperatively (T1), and one month postoperatively (T2).

Feasibility data and field notes were collected by the research coordinators (during recruitment and postoperative follow-up) and by the study lead / research assistants during the intervention period. A postoperative interview explored experiences with prehabilitation into explore the feasibility and practical considerations of virtual prehabilitation for adolescents and young adults with extremity sarcomas.

Prehabilitation to Improve Cancer Surgery Outcomes in AYA Patients With Extremity Sarcomas

Prehabilitation to Improve Cancer Surgery Outcomes in AYA Patients With Extremity Sarcomas (PICaSO-ES): A Proof-of-Concept Trial

Primary exploratory outcome: European Organization for the Research and Treatment of Cancer (EORTC) QLC-C30

Postoperative complication severity and frequency defined according to the Common Terminology Criteria for Adverse Events.

Average postoperative hospitalization period

Total distance traveled during six-minute walk test

Godin Leisure-time Exercise Questionnaire

EQ-5D; All 5 items are rated on a 1 to 3 scale with higher numbers reflecting worse outcomes.

Edmonton Symptom Assessment Scale (ESAS); All 10 items are rated on a 0 to 10 scale with higher numbers reflecting worse outcomes.

Hospital Anxiety and Depression Scale (HADS); All 14 items are rated on a 0 to 3 scale with higher numbers reflecting worse outcomes.

Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F); All 13 items are rated on a 0 to 4 scale with higher numbers reflecting worse outcomes.

Medical Outcomes Study Social Support Scale (SF-20); All item scores transformed into 0 to 100 scales with higher scores reflecting better outcomes.

Experiences in Close Relationships scale (ECR); All 36 items rated on a 1 to 7 scale with higher scores reflecting worse outcomes.

Toronto Extremity Salvage Score (upper or lower)

Defined as the percent of consenting patients based on the total number of otherwise eligible patients (OEP; patients meeting all study eligibility criteria) approached

Defined as the average elapsed time (in days) between diagnosis and extremity sarcoma surgery

Defined as the number and frequency of testing- and intervention-related non-serious adverse events (nSAEs) according to the Common Terminology Criteria for Adverse Events

Defined as percent completion physical testing at baseline and follow-up

Defined as the percent of patients who miss ≥3 consecutive sessions within the intervention period

Defined as the percent of exercise sessions completed based on the total number of sessions prescribed

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Clinico-biological Study/Characterization of Rhabdomyosarcoma in Adolescents and Young Adults, 15-25-year-old Patients	NCT03462888	Rhabdomyosarcom...		15 Years - 25 Years	Centre Oscar Lambret
The Harmonized Interventions to Maintain Health Via Appropriate Risk Factor Modification and Lifestyle Changes in Pediatric, Adolescent and Young Adult Cancer Survivors Pilot Study	NCT04598646	Heart Failure Cardiotoxicity Cancer	Cardio-oncology... Support	18 Years - 45 Years	University Health Network, Toronto
A Phase I Study of Quadrivalent Human Papilloma Virus (HPV) (Types 6, 11, 16, 18) Recombinant Vaccine in HIV-Infected and HIV-Negative Pre-Adolescents, Adolescents, and Young Adults	NCT00798265	Human Immunodef... Human Papilloma... Adolescent Papillomavirus ...	Gardasil Survey	12 Years - 26 Years	National Institutes of Health Clinical Center (CC)
The HIMALAYAS Trial and Lifestyle Changes in Pediatric, Adolescent and Young Adult Cancer Survivors Study: A Multicentre Randomized Controlled Trial	NCT05023785	Heart Failure Cardiotoxicity Cancer	Cardio-oncology...	18 Years - 45 Years	University Health Network, Toronto
The HIMALAYAS Trial and Lifestyle Changes in Pediatric, Adolescent and Young Adult Cancer Survivors Study: A Multicentre Randomized Controlled Trial	NCT05023785	Heart Failure Cardiotoxicity Cancer	Cardio-oncology...	18 Years - 45 Years	University Health Network, Toronto
Prehabilitation to Improve Cancer Surgery Outcomes in AYA Patients With Extremity Sarcomas	NCT04248959	Sarcoma,Soft Ti... Osteosarcoma	Multimodal preh...	18 Years - 39 Years	University Health Network, Toronto
Prehabilitation to Improve Cancer Surgery Outcomes in AYA Patients With Extremity Sarcomas	NCT04248959	Sarcoma,Soft Ti... Osteosarcoma	Multimodal preh...	18 Years - 39 Years	University Health Network, Toronto
Supportive Care Needs of Former Child, AYA Cancer Patients, and of Their Parents: Evaluation During Long-term Follow-up	NCT04711733	Solid Tumor or ...	Interview Self-report que... Medical consult...	6 Years - 31 Years	Centre Leon Berard
Supportive Care Needs of Former Child, AYA Cancer Patients, and of Their Parents: Evaluation During Long-term Follow-up	NCT04711733	Solid Tumor or ...	Interview Self-report que... Medical consult...	6 Years - 31 Years	Centre Leon Berard

Spots Global Cancer Trial Database for adolescents and young adults