Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Blood and Lymph Conditions

Immune System Diseases

Digestive System Diseases

Rare Diseases

Breast Neoplasms

Lymphoma

Head and Neck Neoplasms

Lymphoproliferative Disorders

Colorectal Neoplasms

Carcinoma

Carcinoma in Situ

Breast Carcinoma In Situ

Breast Diseases

Skin Diseases

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Lymphatic Diseases

Immunoproliferative Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Lymphosarcoma

participants randomized to the intervention arm will complete a virtual 8 week exercise and education program.

CaRE@Home intervention

charmaine silva, MSc

Jennifer Jones, PhD

Pragmatic hybrid type 1 effectiveness-implementation (E-I) trial of a virtual cancer rehabilitation program: The study team will conduct a multi-center hybrid type I effectiveness-implementation study to examine the clinical effectiveness and implementation potential of an 8-week multidimensional virtual cancer rehabilitation intervention (CaRE@Home) for cancer survivors with identified cancer-related impairments on level of overall disability (primary outcome) and patient reported physical and social functioning, anxiety, work status, quality of life, and physiologic changes (secondary outcomes). The study team will conduct a multi-centre pragmatic randomized controlled trial (RCT) (Vancouver, Toronto, Saint John and St. John's) to evaluate effectiveness and using the CIFR, the study team will identify potential factors that may affect successful implementation and integration of CaRE@Home in different cancer settings.

Comprehensive multidimensional rehabilitation programs that include both exercise and self management education have the potential to concurrently improve a wide range of post treatment side-effects and overall patient function. In 2017, the Cancer Rehabilitation and Canadian Cancer Rehabilitation (CanRehab) Team: Improving the systematic identification, management, and treatment of the adverse effects of cancer.

Survivorship program at Princess Margaret Cancer Centre launched an evidence driven group based multidimensional Cancer Rehabilitation and Exercise program (CaRE@ELLICSR) for patients who have identified cancer-related impairments. The 8-week program integrates a number of evidence-based techniques to sustain behavioural change and consists of weekly1-hr group exercise classes followed by 1-hr self-management skills education delivered by a rehabilitation expert. Participants return for follow-up at 3 and 6 months post-intervention to monitor progress and adapt exercise as needed. CaRE@ELLICSR has resulted in improvements in overall levels of disability, social functioning, distress, and physical activity. Program satisfaction is high, and wait times are within the target of \<1 month. However, access is an issue with \~50% of referred patients unable to participate due to travel distance, transportation costs or competing obligations (unpublished data).

To increase access, a virtual on-line version of the CaRE program (CaRE@Home) was developed using a series of iterative steps proposed by the NCI Research-Tested Intervention Programs.

The CaRE@Home program is currently undergoing single-group feasibility pilot testing (completion Oct 2019, funded by Ontario Institute for Cancer Research). Feasibility outcomes collected to date demonstrate high program acceptability with 95% of referred patients enrolled and 94% program adherence. The final steps of this process are to formally evaluate effectiveness and prepare for real-world implementation, which is the focus of Project Two of this application. If effective, the virtual CaRE@Home program has the potential to extend access to critical cancer rehabilitation services to a greater number of cancer survivors in need. It also has immense potential to be adapted and scaled to other centres that lack the resources required to deliver in-house cancer rehabilitation services. In Project Two the study team will conduct a multi-center hybrid type I effectiveness-implementation study to examine the clinical effectiveness and implementation potential of CaRE@Home for cancer survivors with identified cancer-related impairments.

Principal Research Aims:

Aim 2.1: Test the effectiveness of CaRE@Home vs. usual care (UC) on disability (primary outcome) and patient reported and physiological outcomes (secondary outcomes) at 3-months post-intervention.

Aim 2.2: Conduct a descriptive implementation-focused process evaluation to inform future implementation efforts

Methods The project is a hybrid type 1 effectiveness-implementation (E-I) study. The aim of hybrid trials are to better align research and practice and to provide a pathway for rapidly moving knowledge from research to implementation. In hybrid type 1 studies, the primary aim is to determine effectiveness in the setting where it will be implemented and the secondary aim is to better understand the context for implementation. This methodology promotes the study of implementation as early as possible in the research process and can serve a dual purpose in helping to explain effectiveness results and informing future implementation efforts.

Aim 2.1: Effectiveness evaluation of CaRE@Home (months 36-58) Design: The study team will conduct a multi-centre pragmatic RCT (Vancouver, Toronto, Saint John and St. John's) to evaluate effectiveness. Clinical effectiveness studies place a greater emphasis on external validity and generalizability than efficacy trials and typically include heterogeneous patient populations and settings. Participants will be randomized into CaRE@Home or UC.

Recruitment and Data Collection: Eligible participants will be identified by their oncology team, and provided information about the study along with contact information for the local study team. Depending on timing, the ePSM platform (Project One) may also be used to identify and invite potential participants. Interested patients will be pre-screened by telephone (eligibility tools above), and those who are eligible will be invited to an in-person baseline assessment (T1). Site-specific screening logs will be maintained. At the baseline assessment, participants will provide consent and complete PRO and physiological measures (see below) with a trained assessor. Following the assessment, the research assistant will obtain the randomization assignment. Those assigned to CaRE@Home will be registered into the CaRE@Home platform.

Follow-up assessment for both groups will occur at 8-weeks (T2 immediate post intervention) and 3 months post-intervention (T3). The CaRE@Home group will have an additional 6 months post-intervention (T4) to assess maintenance. Randomization: Permuted block randomization, with stratification by center and on/finished treatment will allocate participants to either CaRE@Home or UC. Randomization will be computer-generated and managed by the Department of Biostatistics at Princess Margaret Cancer Centre.

Description of Study Arms: i) Care@Home is an 8-week program comprised of: 1) weekly e-modules providing interactive education to promote self-management skills; 2) individualized progressive exercise prescription supported with mobile application (PhysitrackTM); 3) wearable technology (FitbitTM) to track activity and sleep; and 4) weekly brief telephone counselling with a member of the rehabilitation team (see Appendix 4 CaRE@Home program elements). Informed by behavior change theory, the program elements aim to provide patients with the knowledge and tools needed to reach and maintain their wellness and exercise goals. Training for health professionals: In person assessments and weekly phone calls will be delivered by a rehabilitation/exercise professional who has experience working with cancer survivors. The exercise professionals will receive comprehensive training and ongoing supervision. Training will be provided by a Motivational Interviewing Network of Trainers certified trainer (Dr. M. Obadia). The training will be videotaped and an online tool box with training resources will be developed to support future scalability. ii) UC will receive usual care and will be asked to complete in-person assessment at T2 and T3. Following T3 assessment, the UC group will be offered the CaRE@Home program.

Data analysis: Demographic and clinical information across all time points will be summarised using descriptive statistics and plotted across all time points. Effectiveness will be assessed on the full set of consented participants in accordance with the intention to treat principle. The primary outcome is the difference in WHODAS 2.0 mean score between CaRE@Home and UC at T3. Differences on secondary outcomes at T3 will also be compared between the two treatment arms using paired t test or paired Wilcoxon rank-sum test. Maintenance of treatment gains in the CaRE@Home group will be analyzed at T4. An estimate of the effect size and parameters and corresponding confidence intervals will be calculated between groups at T3 and over time (within groups). Variability of the main and interaction effects will be examined on the primary clinical outcome (WHODAS 2.0) and each of the secondary outcomes using separate longitudinal analysis models such as mixed model regression and generalized estimating equation models. Sensitivity analysis will be conducted, adjusting for important clinical factors using the regression model. Finally, a cost-utility analysis will be undertaken to estimate the incremental cost per quality-adjusted life year (QALY) of the intervention arm compared to the control arm.

Sample Size: Our sample size calculations is based on 80% power with a two-sided alpha-level at 0.05 and an estimated effect size of 0.4 standard deviation of the primary endpoint.

Assuming attrition of up to 30% and adherence to be 80%, 388 patients will be recruited (or 194 patients per arm). The number of potentially eligible patients across sites is estimated to be 170 patients per month. Based on proposed staffing per site, a maximum of 20 patients can be enrolled per month in Toronto/Vancouver and 10 per site in NB/NFLD. Enrollment is estimated to take 6-7 months. The study team will use multiple strategies to promote retention and prevent attrition.

Aim 2.2: Implementation-focused Process Evaluation (months 30-52) Design: In order to inform the implementation of CaRE@Home, a process evaluation will be conducted and guided by the RE-AIM framework\[88\]. The CFIR will be used to examine context and understand relevant barriers and facilitators across and within CanRehab sites. See Table 3 for Implementation Framework/Process Evaluation Questions and Tools.

Data Collection Tools: Data tools will include interviews/focus groups, surveys, screening logs, observational notes, technical reports, infrastructure review to inform costs as well as staffing and infrastructure requirements. The study team will triangulate the data from the different quantitative and qualitative sources to answer questions developed based on elements of the selected frameworks and summarize our findings.

Data Analysis: Descriptive variables will be presented as means, distributions, and proportions with differences between subgroups compared. Qualitative information from open-ended survey questions, interviews, and research log entries will be transcribed and analyzed using common deductive qualitative analysis techniques\[133\] following the CFIR qualitative data analysis templates. Following this, all transcripts will be coded and additional inductive codes will be added.

Virtual Rehabilitation for Cancer Survivors

Pragmatic Hybrid Type 1 Effectiveness-implementation (E-I) Trial of a Virtual Cancer Rehabilitation Program

measured using the World Health Organization Disability Assessment Schedule 2.0, which is a cross-cultural standardized method for measuring limitations and restrictions on individuals' activities and participation in society. The average scores are comparable to the WHODAS 5-point scale, he total score for WHODAS ranges from 0-100, where a high score indicates major living limitations ((0-0.49) = none, mild (0.5-1.49), moderate (1.5-2.49), severe (2.5-3.49), or extreme (3.5-4).

Demographic details will be collected from participants at the time of initial assessment via an intake questionnaire. There are no scales, only patient reported outcome questions

Measured using the 10-item sub-scale of the short form Health Survey (scale from 0 (negative health) to 100 (positive health))

Measured using the Social Difficulties Inventory. A zero score indicates perfect comparison with consensus group and \> or equal to 2 indicates unacceptable performance/remedial action required.

Measured using the Generalized Anxiety Disorder 7. The overall GAD 7 score ranges between 0-21, with zero meaning no anxiety and 21 meaning severe anxiety.

Measured using the the International Physical Activity Questionnaire - Short Form. It assesses the number of days/time spent on PA in moderate intensity, vigorous intensity, walking of at least 10-min duration the last 7 days, and time spent sitting on weekdays the last 7 days.

measured using the short version of the World Health Organization's Heath and Work Performance Questionnaire. Absenteeism is scored in terms of hours lost per month, which is to say that a high score indicates a higher amount of absenteeism. The measure of absolute absenteeism is expressed in raw hours, with a negative lower bound (if the person works more than expected) and an upper bound equal to the number of hours the respondent is expected to work. The measure of relative absenteeism is expressed as a percentage of expected hours and ranges between a negative number (works more than expected) and 1.0 (always absent).

measured using the EuroQol 5D-5L\[81\], a brief and frequently used measure of health status that consists of a weighted sum of five dimensions: Mobility, Self-care, Usual activities, Pain/Discomfort and Anxiety/Depression, and provides a simple descriptive profile and a single index value for health status.

assessed throughout the study and any adverse events resulting from the intervention will be scored on the CTCAE version 5.0\[82\] and documented during the health coaching calls and physical assessments with the exercise professional.

Participant weight at all physical assessments (T1, T2, T3, T4) will be collected. The data will inform calculations for BMI.

Measured with the six minute walk test (6MWT)

Physiological measure of muscular strength measured with hand grip strength and measured bilaterally with standard Jamar dynamometer.Per CSEP protocol, an average of 2 trials with a 2 min rest in-between trials will be taken. The best of the left and right hand will be taken as the overall grip score. Participant handedness will also be recorded.

Physiological measure of endurance is measured with the 30-second sit to stand test for lower body strength

Measured with the 4-meter Gait speed test

University Health Network, Toronto

Symptoms and General Pathology

Mouth and Tooth Diseases

Recurrence

Esophageal Neoplasms

Carcinoma, Squamous Cell

Mouth Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Esophageal Diseases

Mouth Diseases

Stomatognathic Diseases

Esophageal Cancer

Oral Cancer

Antineoplastic Agents

All Drugs and Chemicals

Vasodilator Agents

Urological Agents

Nivolumab

Pembrolizumab

Immunomodulating Agents

Tadalafil

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Phosphodiesterase 5 Inhibitors

Phosphodiesterase Inhibitors

Enzyme Inhibitors

Tadalafil for up to 12 months and pembrolizumab for up to 24 months.

Khushbu Singh

Joseph Califano

This study will examine the combination of pembrolizumab and tadalafil for safety and efficacy in advanced head and neck cancer.

Immune competent animal models of HNSCC demonstrate that combination PDE-5 inhibitor (tadalafil) and PD-1 inhibitor therapy is more effective than either therapy alone based on the concept of targeting multiple immune repressive abnormalities simultaneously (PD-1 checkpoint and myeloid suppressive pathways).

This trial will test the hypothesis that combination PD-1 inhibition and PDE-5 inhibition can be safely co-administered, and secondarily test the hypothesis that the combination of both therapies will be more effective than PD-1 inhibition alone in recurrent/metastatic HNSCC.

Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Cancer

A Phase II Study of Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Rate of dose limiting toxicity at least possibly attributable to study treatment

Overall survival at 12 months post-enrollment

University of California, San Diego

Professor of Medicine

Patients enrolled in Arm A will receive IPI-549 40 mg by mouth daily for at least 14 days

40mg by mouth (PO) every day (QD) for at least 14 days

IPI-549

Debanjali Ghosh, MA

Elaine Eng

Ezra Cohen, MD

The purpose of this study is to investigate how effective the study drug IPI-549 is against types of cancers. IPI-549 is considered experimental because it is not approved by the US Food and Drug Administration (FDA) for the treatment of cancer.

Patients will be treated with 2 weeks of IPI-549, a specific PI3Kγ inhibitor. Tumor tissue for research purposes through core biopsies will be obtained prior to initiation of IPI-549 and at surgery.

This is a phase 2 window of opportunity trial in patients with locally advanced head and neck cancer. A key objective is to provide the first proof that macrophage phenotype switching can be accomplished in humans and lay the groundwork for future trials of this novel approach to immune therapy. Patients who are candidates for surgical resection will be enrolled and treated with 2 weeks of IPI-549, a specific PI3Kγ inhibitor. Tumor tissue for research purposes through core biopsies will be obtained prior to initiation of IPI-549 and at surgery.

The study team hypothesizes that mRNA signatures of immune response will be increased in IPI-549-treated patients. For the efficacy endpoints, RECISTv1.1 will be used.

Window of Opportunity Study of IPI-549 in Patients With Locally Advanced HPV+ and HPV- Head and Neck Squamous Cell Carcinoma

Phase 2 Window of Opportunity Study of IPI-549 in Patients With Locally Advanced HPV+ and HPV- Head and Neck Squamous Cell Carcinoma

To detect IPI-549-induced changes in PI3Kγ-regulated signatures of immune suppression.

Compare pre- vs. post-treatment tumor tissue

T cell receptor (TCR) sequencing at baseline, surgery, end of treatment or at time of disease progression.

To determine safety and tolerability of IPI-549 and change in tumor size in patients with locally advanced HNSCC

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Virtual Rehabilitation for Cancer Survivors	NCT05898789	Breast Cancer, ... Colorectal Canc... Head and Neck C... Lymphoma Breast Cancer S... Breast Cancer S... Breast Cancer S... Colorectal Canc... Colorectal Canc... Head and Neck C... Head and Neck C... Lymphoprolifera...	CaRE@Home inter...	18 Years -	University Health Network, Toronto
Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Cancer	NCT03993353	Head and Neck C... Head and Neck S... Head and Neck C... Head and Neck C... Head and Neck C... Head and Neck C... Cancer Cancer of Esoph... Cancer, Metasta... Cancer of Head ... Cancer of Mouth Cancer of Neck	Pembrolizumab Tadalafil	18 Years -	University of California, San Diego
Window of Opportunity Study of IPI-549 in Patients With Locally Advanced HPV+ and HPV- Head and Neck Squamous Cell Carcinoma	NCT03795610	Head and Neck S... Head and Neck C... Head and Neck C... Head and Neck C... Head and Neck C... HPV-Related Car... HPV-Related Mal... HPV-Related Squ...	IPI-549	18 Years -	University of California, San Diego

Spots Global Cancer Trial Database for head and neck cancer stage iii