Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Heart and Blood Diseases

Rare Diseases

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Melphalan

* Two 8 oz. bottles of Enterade will be administered daily
* Enterade will be given orally from admission until day +14 or until discharge
* Standard Supportive Care will be administered according to institution's practice

* Two 8 oz. bottles of Placebo will be administered daily
* Placebo will be given orally from admission until day +14 or until discharge
* Standard Supportive Care will be administered according to institution's practice

Enterade

Placebo

Standard Supportive Care

Mahasweta Gooptu, MD

This research study is evaluating Enterade, a supplement, as a possible treatment for the side effects caused by Stem Cell Transplant.

The following interventions will be involved in this study:

* Enterade plus standard supportive care
* Placebo plus standard supportive care. The placebo will be a mixture of water, electrolytes, and sweetener.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease, or in this case, the side effects from a standard treatment for Stem Cell Transplant side effect. "Investigational" means that the intervention is being studied.

In this research study, the investigators are evaluating Enterade/Placebo plus standard supportive care for the treatment of the side effects caused by transplant. Enterade works by rehydrating the intestinal cells, thereby helping to restore normal bowel function. The ingredients in Enterade are generally recognized as safe by the Food and Drug Administration. This research study is hoping to learn if adding Enterade to the standard supportive care regimen for the participant transplant will help reduce the side effects from the transplant.

A Study Evaluating a Proprietary Amino Acid Mixture (Enterade®) in Patients Receiving High-Dose Melphalan Conditioning Followed by Autologous Stem Cell Transplantation for Multiple Myeloma and Non-Hodgkin Lymphoma

A Randomized Double-Blinded Phase 2 Study Evaluating a Proprietary Amino Acid Mixture (Enterade®) in Patients Receiving High-Dose Melphalan Conditioning Followed by Autologous Stem Cell Transplantation for Multiple Myeloma and Non-Hodgkin Lymphoma

Evaluation will made using Fisher's exact test. Among 99 participants who received some intervention

Entrinsic Health

Dana-Farber Cancer Institute

Principal Investigator

The primary endpoint is the incidence of NCI-CTCAE 4.0 grade 3 or higher GI toxicity in the 14 days following autologous HSCT

* Two 8 oz. bottles of Enterade will be administered daily
* Enterade will be given orally from admission until day +14 or until discharge
* Standard Supportive Care will be administered according to institution's practice

Enterade

Standard Supportive Care

Enterade and Standard Supportive Care

* Two 8 oz. bottles of Placebo will be administered daily
* Placebo will be given orally from admission until day +14 or until discharge
* Standard Supportive Care will be administered according to institution's practice

Placebo

Standard Supportive Care

Placebo and Standard Supportive Care

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Count of participants

Kelly Masone

Only 17 participants met the protocol definition of compliance

Number of Participants With Grade 3 or Higher Diarrhea GI Toxicity

Day +1 to Day +7

Day +8 to Day +14

Maximum Daily Stool Frequency

Percentage of Participants With Diarrhea on the Day of Maximum Daily Stool Frequency

Duration Of Hospitalization (Days) From Admission To Discharge

Percent Change in Weight From Baseline to Day 14

Median Amount Of Anti-Diarrheal Medications

Patients who take the study drug two 8 oz. bottles (480 ml) daily for at least 11 days are regarded as compliant. Compliance is assessed among patients who received any amount of the study drug (N=99).Only 17 participants met the protocol definition of compliance

the Tolerability of Enterade® as Measured by the Number of Compliant Patients

Admission

D+14

Calorie Consumption

Fever

Neutrophil count decreased

Number of Participants With Fever or Neutropenia

Overall Study

Supportive care for the patient and caregiver will be provided by the outpatient palliative care team which includes clinicians with specialized palliative care training, social workers, spiritual care specialists and mental health clinical nurse specialist.

Structured palliative care

Supportive care for the patient and caregiver will be provided by the treating oncologist.

Standard supportive care

Michelle Treasure, MD

The goal of this research study is to find out if providing patients who are enrolled in phase 1 clinical trials with structured supportive care will enable them to continue in the Phase 1 trial longer and improve their quality of life by reducing or treating side effects and by providing emotional and social support to the patient and family. The structured supportive or palliative care intervention will be provided by a team of trained specialists which include doctors, nurses, social workers and spiritual care providers. The supportive care team will provide treatment to address symptoms, such as pain or anxiety, caused by the cancer itself or from the treatment. The team can make referrals to other specialists. Such as psychologists or nutritionist, if needed, and can help arrange for services to address home care needs.

Primary Objective(s): To assess symptoms, adverse events, duration on study, reason for study discontinuation, and quality of life among patients participating in phase I clinical trials who receive structured palliative care, and those who receive standard supportive care. Duration on study will serve as the primary objective for sample size determination.

Secondary Objective(s):

1. To describe the quantity (e.g. hours), type, and cost of palliative care personnel services used by patients and caregivers receiving structured palliative care.

Exploratory:

1. To compare adverse event profiles, duration on study, and quality of life between patients who receive structured palliative care and those receiving standard supportive care.
2. To compare caregiver burden and quality of life between the study arms.

A Pilot Study of Structured Palliative Care for Patients Enrolled on Phase I Clinical Trials

Change in patient symptom burden when compared to baseline between patients who received structured palliative care and those who received standard supportive care

Change in quality of life when compared to baseline between patients who received structured palliative care and those who received standard supportive care

Change in caregiver burden when compared to baseline between those who received structured palliative care and those who received standard supportive care

Change in caregiver quality of life as assessed through change in QOLLTI-F score when compared to baseline between those who received structured palliative care and those who received standard supportive care

Measure of central tendency for why patients discontinued the phase I study. Patient reported outcomes for reason for study discontinuation will be qualitatively assessed

Measure of central tendency of the duration patients were on the phase I study. Duration on study will serve as the primary objective for sample size determination

Measure of central tendency of adverse events. AE will be described and further categorized as modifiable (primary symptom experience) and non-modifiable (laboratory abnormalities). The influence of adverse events on study outcomes particularly duration on study and reason for study discontinuation will be assessed. An exploratory weighted adverse event score will be calculated using the equation: adverse event score = ∑ (NAE \* GAE) where N denotes the adverse event number, G denotes grade, AE denotes adverse event. These scores will be compared between study arms

Mean number of hours utilized by patients and caregivers who received structured palliative care. This analysis will be descriptive, reporting measures of central tendency

Measure of central tendency for the type of palliative care services utilized by patients and caregivers who received structured palliative care. This analysis will be descriptive, reporting measures of central tendency

Case Comprehensive Cancer Center

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Intervention Strength/aerobic exercise, weights, bike or treadmill

Intervention Aerobic exercise, bike or treadmill

Group 1) includes strength exercise of the large muscle groups (2-3 sets, 8-12 repetitions on an intensity of 80 % of 1-RM) and 3x3 min high intensity aerobic exercise (16-18 on Borg scale) on an exercise bike or treadmill twice a week for 16 weeks

Resistance and aerobic training

Group 2) includes aerobic exercise on an exercise bike or treadmill, 20 min moderate intensity (13-15 on Borg scale), and 3x3 min high intensity (16-18 on Borg scale) twice a week during 16 weeks

Aerobic training

Yvonne Wengstrom, Professor

This study on women with breast cancer during and after chemo- and hormonal therapy compares the effect of different physical training programs on physical and mental well-being and systemic inflammation mechanisms in blood. In a sub-group of participants, mitochondrial biogenesis and function and other molecular processes in skeletal muscle biopsies are studied. The women will be randomly allocated into three different intervention arms, a control arm with usual care and two different training arms. All participants will respond to questionnaires and have blood samples and taken and for a subgroup muscle biopsies before and after the exercise intervention. Participants will be supported to uphold exercise through collaboration with Friskis \& Svettis and followed for 5 years. Some of the women will also be asked to participate in an in depth interview about the experiences of exercise during ongoing treatment. This study will contribute to increased knowledge about the type, intensity and frequency of training that patients with breast cancer benefit most from with regards to impact on physical and mental wellbeing. This knowledge is of great importance since experience shows that patients and relatives often seek information about rehabilitation, self-care and physical activity. The study will also contribute to the improvement of the patients´ quality of life, ability to return to work, and reduce social costs, but above all, increase the possibility for development and implementation of evidence-based rehabilitation of women with breast cancer during and after active treatment.

Purpose The main aim is to, in women undergoing chemotherapy for breast cancer, explore how different training interventions impact physical capacity and psychological well being.

Research questions

* Does PA improve the ability to return to work after breast cancer treatment is completed?
* How do women with breast cancer during chemotherapy treatment respond to controlled and supervised aerobic fitness training and a combination of aerobic fitness training and strength training in physiological, structural and molecular outcome measures such as muscular strength, aerobic fitness, muscle mass, mitochondrial density, gene activity in muscle and B-Hb, s-CRP and other blood variables,?
* Is there a difference between the women in the aerobic exercise training group, the combined aerobic and strength-training group and the control group regarding symptom distress and health related quality of life?
* Are there any effects of exercise training on chemotherapy completion and hospitalization rates?
* Is adherence to physical exercise impacted by the individuals' personality?
* Are there any remaining effects of the physical exercise intervention, on cardiotoxicity, cognitive function, survival and morbidity, up to 5 years after treatment is completed?
* Is the intervention cost-effective?

Study design and methods Participants A total of 240 women will be recruited from the Department of Oncology Breast and Sarcoma units at Radiumhemmet and Södersjukhuset, Karolinska University Hospital.

Inclusion criteria: patients up to 70 years with breast cancer Stage I-IIIa before the start of chemotherapy. Exclusion criteria: patients with advanced disease, patients where physical activity is considered contraindicated because of medical reasons such as heart or lung disease, brain or bone metastases, cognitive dysfunction, and patients who do not speak or understand the Swedish language.

Randomization The Clinical Trials Unit (KPE) at Radiumhemmet, Karolinska Universitetssjukhuset, conducts inclusion to the study and randomization. The participants are allocated to either two different training groups or a control group. The participants are also randomized to a muscle biopsy (n=45) before and after the intervention.

Group 1) includes strength training of the large muscle groups (2-3 sets, 8-12 repetitions on an intensity of 80 % of 1-RM) and 3x3 min high intensity aerobic exercise (16-18 on Borg scale) on an exercise bike or treadmill twice a week for 16 weeks.

Group 2) includes aerobic exercise on an exercise bike or treadmill, 20 min of moderate intensity (13-15 on Borg scale), and 3x3 min high intensity aerobic exercise (16-18 on Borg scale) twice a week during 16 weeks.

Group 3) control group, will get standard information around physical activity during treatment but no supervised training.

Data Collection Data will be collected for all study participants regarding demographics and diagnosis, cancer treatment, laboratory and sick leave data (patient-reported), relapse, survival, co-morbidity and cause of death in relevant registers.

* Data collection of demographic data occurs before (before randomization) and after the intervention, and at three time points: 1 year, 2 years and 5 years after treatment is completed. Baseline is about 5 weeks after surgery and before initiation of chemotherapy.
* All participants that accept participation in the study will undergo a resting ECG examination and will provide responses to a small, targeted set of heart disease history questions.
* Muscular strength is measured with the instrument JAMAR that is a dynamometer, measuring muscle strength in the hand. Lower limb muscle strength is measured through isometric mid-thigh pull. This is assessed in all study participants at all time points: before and the intervention, year 1, 2, and 5.. The instruments have good reliability and validity.
* Before and after the intervention aerobic fitness (VO2-max) of the participants in the intervention groups will be assessed with a submaximal exercise test. This will be measured at all time points: before and the intervention, year 1, 2, and 5.
* Algometry, to measure pain sensitivity will be performed at time points: before and after the intervention, year 2 and 5.
* Chemotherapy completion, hospitalization, hemoglobin-, lymphocyte- and platelet concentrations during chemotherapy will be extracted from the patients' medical records.
* Blood sampling and muscle biopsy procedures will take place at the KPE lab Radiumhemmet, Karolinska University Hospital, Solna. Muscle biopsies will be obtained under local anesthesia in the m. vastus lateralis (approximately 100 mg) with a Bergström needle. This takes place before the intervention starts and 48-72 hours after the last training session. Mitochondrial density and muscle morphology will be analyzed. Venous blood is sampled at time points: before and the intervention, year 1, and 5, for analysis of white cell distribution, for markers of systemic inflammation, and markers of cardiac damage
* Physical activity level and energy consumption is determined by ActiGraph GT3X (Actigraph). Actigraph is a combined heart rate sensor and accelerometer that continuously collects data. The method has been previously tested and is shown to have good reliability and validity. In this project all the participants in the three groups will be carrying an Actigraph for seven days, before the intervention. An Activity Diary for daily subjective reporting of physical activity will also be used during the intervention period.

Instruments

* Piper Fatigue Scale assesses fatigue in four dimensions. The scale has been shown to have psychometric properties that are reliable for assessing subjective dimensions of fatigue among Swedish populations of cancer patients. Data will be collected for all study participants (intervention and control) before randomization and after the intervention, and at 1 year, 2 years and 5 years after treatment.
* Memorial Symptom Assessment Scale (MSAS) assesses 32 common cancer-related symptoms. The instrument is validated for Swedish patients with breast cancer. Data will be collected for all study participants before randomization and after the intervention, and at 1 year, 2 years and 5 years after treatment.
* EORTC QLQ-C30 is a cancer-specific instrument that measures health-related quality of life in terms of physical, emotional, social, cognitive and everyday function. Data will be collected for all study participants before randomization and after the intervention, and at 1 year, 2 years and 5 years after treatment.
* Sense of coherence (SOC) is a questionnaire, which shows how a person sees the world and his own life as comprehensible, manageable and meaningful. Individuals with a strong sense of coherence are able to mobilize the resources to manage their health during illness and treatment. SOC short version consists of l3 questions that all participants complete once before the start of treatment. The Swedish version of the SOC-13 has been shown to have good validity and reliability. It has also demonstrated high internal consistency.
* The Amsterdam Cognition Scan- an online neuropsychological test battery that measures a broad variety of cognitive functions, measured five years following inclusion to the exercise intervention
* Echocardiogram- to measure cardiac function, five years following inclusion to the exercise intervention

Qualitative interviews

• Individual interviews about/around the experience of physical activity associated with chemotherapy treatment will be carried out with 15 participants. An open question will be asked, such as "Can you describe how you experienced the period of training?". Because of the nature of this question, the women will have the freedom to narrate their stories, and the interview will focus on elements that surface as significant. Supplementary questions will be asked to create depth and further understanding of the phenomena.

Data Analysis Muscle and blood analysis: From 45 participants in the project, we plan to take a muscle biopsy before and after the training intervention. The molecular exercise physiology lab is fully equipped to store muscle biopsies and other biological material. Many methods are set-up in our muscle lab and others are performed in different core facilities. Molecular and biochemical analyses: Skeletal muscle biopsy samples are obtained with the percutaneous needle technique. Analysis of protein content, CS activity, and immunohistochemistry will be performed.

Quantitative Collected quantitative data will be analysed using parametric statistics for normally distributed data and non-parametric statistics for non-normally distributed data. Subgroup analysis will be conducted with a focus on the type of treatment. Power Calculation: variable cancer related fatigue, selected significance level 0.05, power 0.80 = 240 patients will be recruited in total to detect a statistical difference with medium effect size.

Qualitative Qualitative data from individual interviews with 15 patients will be analyzed inductive with content analysis.

Workplan Data collection is currently ongoing and 80 patients are included in the study. With the current inclusion rate the 240 participants will be included by the end of 2015.

To support the women to uphold PA after treatment is completed a collaboration has been initiated with Friskis \& Svettis in Stockholm, during the five year follow up period this will encompass FaR (physical activitiy receipt) and invitations to motivational healthy life style sessions three times a year, the sessions will also include information on longterm effects/symptoms of treatment and support with self care.

OptiTrain - Optimal Training Women With Breast Cancer

OptiTrain - Optimal Training for Women With Breast Cancer During Chemotherapy Treatment

Relative dose intensity extracted from medical records

Hospitalizion rates during chemotherapy extracted from medical records

Neutrophil, lymphocyte, hemoglobin, and platelet concentrations extracted from medical records

Quality adjusted life years based on EORTC-QLQ-C30 (EORTC-8D)

neuropsychological test consisting of 7 computerized online cognitive tests measuring a broad range of cognitive domains, including attention, verbal memory and executive functioning. The score range is between -15 to 50. A higher score indicates a better outcome.

ECG to assess abnormalities such as left ventricular hypertrophy and/or arrhythmias

Karolinska Institutet

OCN, PhD, Professor of Nursing

Antirheumatic Agents

Hematinics

Anti-Infective Agents

Paclitaxel

Albumin-Bound Paclitaxel

Trastuzumab

Pertuzumab

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Liver Extracts

Tubulin Modulators

Antimitotic Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Patients aged 18 to 40 in good physical condition Eastern Cooperative Oncology Group (ECOG) scale 0-1, who are set to receive neoadjuvant chemotherapy will be selected. Criteria for entry into the study include proper liver, kidney and bone marrow function as well as heart ejection fraction of ≥ 50%. Treatment will be carried out according to 4 x AC regimen (doxorubicin 60 mg/ m2 cyclophosphamide 600 mg/ m2 i.v. every 21 or every 14 days + pegfilgastrim) followed by 12 x paclitaxel 80 mg/ m2 every 7 days and in the case of HER2 positive tumors trastuzumab ± pertuzumab (according to SPC).

The group in which, concurrently with chemotherapy,IPA will be ordered, by means of supervised high intensity interval training twice a week.

During the course of chemotherapy, the intensity of physical activity will be increasing.

HIIT training twice a week throughout the chemotherapy: treadmill, elliptical, stationary bicycle and indoor rower. The intensity of physical activity will be increasing during consecutive mesocycles. Each training session will begin with a 10-min. wole-body warm-up session at 50-60% hear rate (HR) max. Mesocycle 1 - one month with 4 sets of 1 min. 45 sec. of exercise at a maximal intensity of 75% HR max. Mesocycle 2 with exercises at 80% to 90% HR max divided into 3 periods: 1/ one month, session of 5 sets 1 min. 30 sec. each; 2/ two months, sessions of 5 sets 1 min. 45 sec. each; 3/ two months, sessions of 5 sets 2 min. each. Moreover patients will be instructed to individually perform- a 45-min. aerobic training session (e.g.: walking, jogging, roller skating, swimming) once a week, in patient's own time.

High Intensity Interval Training (HIIT)

Patients aged 18 to 40 in good physical condition (Eastern Cooperative Oncology Group (ECOG) scale 0-1) who are set to receive neoadjuvant chemotherapy will be selected. Criteria for entry into the study include proper liver, kidney and bone marrow function as well as heart ejection fraction of ≥ 50%. Treatment will be carried out according to 4 x AC regimen (doxorubicin 60 mg/ m2 cyclophosphamide 600 mg/ m2 i.v. every 21 or every 14 days + pegfilgastrim) followed by 12 x paclitaxel 80 mg/ m2 every 7 days and in the case of HER2 positive tumors trastuzumab ± pertuzumab (according to SPC).

neoadjuvant treatment (doxorubicin, cyclophosphamide, paclitaxel, trastuzumab, pertuzumab)

Patients will be asked to perform 150-300 min. of moderate-intensity aerobic activity or 75-150 min. of vigorous aerobic activity. Each participant will be monitored by an activity watch worn at all times by the patient.

Maria Litwiniuk, Prof

Joanna Kufel-Grabowska, MD, PhD

Maciej Górecki, PT, PhD

The main goal of this study is to assess the impact of supervised intense physical activity (IPA) on outcomes of neoadjuvant chemotherapy in young women with breast cancer (YWBC). In this project standard neoadjuvant chemotherapy will be used concordant with summary of product characteristics (SPC). However during treatment (including days of chemotherapy application) an additional modifier of therapy will be carried out in the form of intense physical activity. This strategy is not recognized in SPC. This project aims to improve the results of breast cancer treatment in young women. According to available data, nowadays this subset of breast cancer patients has worse therapy results in comparison to older women. This is partially because of the different tumor characteristics; young women are more likely to present with human epithelial growth factor receptor 2 (HER2) receptor overexpression or with triple negative breast cancer. In the treatment of YWBC, preoperative chemotherapy is most often the first step. This enables the opportunity to assess the effectiveness of additional interventions in a mode it was never tested before. It is believed that physical activity improves the results of breast cancer treatment, however there are only few reports describing its benefit and role in terms of preoperative chemotherapy.

In the current project, the investigators planned to introduce supervised increased physical activity concurrently with neoadjuvant treatment in YWBC at early stage of disease. The main goal of the study is to assess the effect of physical activity on preoperative chemotherapy outcomes. The change of tumor size after neoadjuvant chemotherapy, as well as the impact on Quality of Life (QoL) and Patients' Reported Outcome (PRO) in described above treatment modality. Secondary endpoints are the following: the pathologic Complete Response (pCR), disease free survival after 3 years (3-yr DFS), overall survival (OS), cardiotoxicity of treatment, the effect of physical activity on tumor microenvironment and Ki67 as well as the impact of increased physical activity on further patients' lifestyle changes.

The main goal of this study is to assess the impact of supervised intense physical activity (IPA) on outcomes of neoadjuvant chemotherapy in young women with breast cancer (YWBC). In this project standard neoadjuvant chemotherapy will be used concordant with summary of product characteristics (SPC). However during treatment (including days of chemotherapy application) an additional modifier of therapy will be carried out in the form of intense physical activity. This strategy is not recognized in SPC. This project aims to improve the results of breast cancer treatment in young women. According to available data, nowadays this subset of breast cancer patients has worse therapy results in comparison to older women. This is partially because of the different tumor characteristics; young women are more likely to present with human epithelial growth factor receptor 2 (HER2) receptor overexpression or with triple negative breast cancer. In the treatment of YWBC preoperative chemotherapy is most often the first step. This enables the opportunity to assess the effectiveness of additional interventions in a mode it was never tested before. It is believed that physical activity improves the results of breast cancer treatment, however there are only few reports describing its benefit and role in terms of preoperative chemotherapy.

In the current project the investigators planned to introduce supervised increased physical activity concurrently with neoadjuvant treatment in YWBC at early stage of disease. The main goal of the study is to assess the effect of physical activity on preoperative chemotherapy outcomes. The change of tumor size after neoadjuvant chemotherapy, as well as the impact on Quality of Life (QoL) and Patients' Reported Outcome (PRO) in described above treatment modality. Secondary endpoints are the following: the pathologic Complete Response (pCR), disease free survival after 3 years (3-yr DFS), overall survival (OS), cardiotoxicity of treatment, the effect of physical activity on tumor microenvironment and Ki67 as well as the impact of increased physical activity on further patients' lifestyle changes. Patients aged 18 to 40 in good physical condition Eastern Cooperative Oncology Group (ECOG) 0-1 who are set to receive neoadjuvant chemotherapy will be selected. Criteria for entry into the study include proper liver, kidney, and bone marrow function as well as heart ejection fraction ≥ 50%. Treatment will be carried out according to 4 x AC regimen (doxorubicin 60 mg/ m2 cyclophosphamide 600 mg/ m2 i.v. every 21 or every 14 days + pegfilgastrim) followed by 12 x paclitaxel 80 mg/ m2 every 7 days and in the case of HER2 positive tumors trastuzumab ± pertuzumab (according to SPC).

After receiving patients' agreement and signing informed consent form, the patient will undergo testing by a multidisciplinary panel of physicians. A cardiological assessment will be completed along with spiroergometry, bone density and anthropometric measurements. The patient will be asked to complete surveys assessing their QoL together with reporting their previous activity level and everyday functioning. Patients will be randomized into two groups - the comparator group undergoing chemotherapy and the intervention group in which additional intervention IPA will be ordered, in means of supervised high intensity interval training twice a week. Modalities of exercise will include: treadmill, elliptical, stationary bicycle and indoor rower. During the course of chemotherapy, the intensity of physical activity will be increasing. Moreover, throughout the entire therapy time, a 45-minute aerobic training session (e.g.: walk, jogging, roller skates, swimming) will be introduced once a week. In the control group, patients will be asked to independently perform their physical activity at an intensity and volume specified in general guidelines: 150-300 min. of moderate-intensity aerobic activity or 75-150 min. of vigorous aerobic activity. Each participant will be monitored at all times by the use of a standard biologic activity recording device.

After the administration of anthracycline, the following procedures will be done: tumor/tumor bed core needle biopsy, mammography, breast ultrasound and cardiological assessment. Following the completion of chemotherapy all testing will be repeated with the exception of bone density measurement and core biopsy. These tests will be repeated one year after surgery. In addition, patients will be assessed for their immune status before and after chemotherapy, as well as one year of observation. When tissue material is available an assessment of the composition of inflammatory infiltrate will be performed using immunohistochemical stainings for immune cell markers. The investigators also planned to preserve material taken from the primary tumor and possible metastasis for molecular analysis (next generation sequencing (NGS), microarrays). The observation will be carried out for 10 years with own resources.

Patients will be randomized into two groups. Patients which are set to receive neoadjuvant chemotherapy will be selected. Treatment will be carried out according to 4 x AC regimen (doxorubicin 60 mg/ m2 cyclophosphamide 600 mg/ m2 i.v. every 21 or every 14 days + pegfilgastrim) followed by 12 x paclitaxel 80 mg/ m2 every 7 days and in the case of HER2 positive tumors trastuzumab ± pertuzumab (according to SPC).

The group in which additional intervention IPA will be ordered, in means of supervised high intensity interval training twice a week. During the course of chemotherapy, the intensity of physical activity will be increasing. Moreover, throughout the entire therapy time, there will be introduced a 45-minute aerobic training session (e.g.: walk, jogging, roller skates, swimming) ones a week. In the control group patients will be asked to independently continue their regular physical activity same as prior to the oncologic treatment.

Supervised Physical Activity in Young Women With Early Breast Cancer During Neoadjuvant Chemotherpy

Score based on the QLQ-BR23 questionnaire which includes the following scales: body image (score range 4-16), sexual functioning (score range 2-8), systemic therapy side effects (score range 7-28), breast symptoms (score range 4-16), arm symptoms (score range 3-12), sexual enjoyment (score range 1-4), future perspectives (score range 1-4), being upset by hair loss (score range 1-4); higher score meaning worse outcome (higher level of symptomatology or lower level of functioning).

complete pathological response (pCR, pathologic Complete Response)

A change in LVEF \>10 percentage points, to a value below 50%.

For patients with acute onset dyspnea increase \<100 pg/ml, for patients with slow increase in breathlessness increase \>35 pg/ml.

Daily number of steps measured throughout the intervention using an activity watch.

Measured during physical activity using an activity watch.

Measured throughout the intervention using an activity watch.

Daily number of minutes spent actively measured using an activity watch.

Daily number of minutes of sleep measured using an activity watch.

Score based on Acceptance of Illness Scale, a single scale with range of points 8-40, with a higher score meaning better acceptance of one's medical condition.

Assessment of the percentage of immune cells infiltrating the tumor based on immunohistochemical staining of paraffin sections of a tumor. Staining will include the following markers: CD45, CD8, CD4 to assess absolute inflammatory cells, cytotoxic T cells, and helper T cells. The infiltrating cells will be measured as an area occupied by inflammatory cells over total area, and will be expressed as a percentage.

Ki67 will be assessed based on immunohistochemical staining of paraffine section of a tumor. Ki67 index will be measured as a number of ki67-positive cells over the total number of invasive cells, and will be expressed as a percentage.

The Greater Poland Cancer Centre

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Digestive System Diseases

Ear, Nose, and Throat Diseases

Mouth and Tooth Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Recurrence

Pain

Small Cell Lung Carcinoma

Deglutition Disorders

Esophagitis

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Esophageal Diseases

Gastrointestinal Diseases

Pharyngeal Diseases

Otorhinolaryngologic Diseases

Gastroenteritis

Small Cell Lung Cancer

Analgesics

Central Nervous System Depressants

Anti-Arrhythmia Agents

Channel Blockers

Gastrointestinal Agents

Oxycodone

Lidocaine

Aluminum hydroxide, magnesium hydroxide, drug combination

Patients swallow 10 cc (approximately 2 level teaspoons) of liquid Manuka honey 4 times per day while awake over an approximately 12 hour period (e.g. 8 a.m., Noon, 4 p.m., and 8 p.m.) 7 days/week during concurrent chemotherapy and radiation treatment.

Manuka honey in liquid form

Patients place 2 lozenges (the equivalent of 10 cc of liquid Manuka honey), one at a time, in the mouth, allowing each lozenge to dissolve on the tongue/in the mouth, swallowing the honey as it dissolves. Patients do this 4 times per day while awake over an approximately 12 hour period (e.g. 8 a.m., Noon, 4 p.m., and 8 p.m.) 7 days/week during concurrent chemotherapy and radiation treatment.

Manuka honey in lozenge form

Patients receive standard supporting care for esophagitis-related pain as needed during concurrent chemotherapy and radiation treatment. The following regimen is recommended, but the local standard of care is permitted.

1. A compound containing viscous lidocaine and magnesium aluminum oxide (Maalox®);
2. Liquid or solid oxycodone, 5-10 mg, every 3 hours as needed.

Lawrence B. Berk, MD, PhD

RATIONALE: Manuka honey may prevent or reduce esophagitis-related pain caused by chemotherapy and radiation therapy. It is not yet known whether Manuka honey is more effective than standard care in preventing pain.

PURPOSE: This randomized phase II clinical trial is studying Manuka honey to see how well it works in preventing esophagitis-related pain in patients receiving chemotherapy and radiation therapy for lung cancer.

OBJECTIVES:

Primary

* Evaluate the relative efficacy of 4 times a day consumption of liquid or lozenge Manuka honey to delay or prevent radiation esophagitis-related pain (during combined chemotherapy and radiation therapy for lung cancer) as compared to standard supportive treatment, as measured at week 4 by Numerical Rating Pain Scale (NRPS) for pain upon swallowing.

Secondary

* Evaluate the trend of severity of radiation esophagitis-related pain during combined chemotherapy and radiation therapy for lung cancer using weekly measurements of the NRPS.
* Evaluate the adverse events associated with Manuka honey, as measured by CTCAE, v. 4.
* Evaluate the severity of radiation esophagitis (grade 3-4, CTCAE, v. 4).
* Assess weight loss (percent weight change from baseline to 4 weeks).
* Assess quality of life (QOL) and pain, as measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-30) global QOL score and pain symptom subscale.
* Assess patient-reported dysphagia via a daily patient log.
* Assess nutritional status, as measured by the mean change in serum prealbumin levels from baseline to 4 weeks.
* Assess opioid use by collecting the patient's narcotic use in the previous 24-hour period at each weekly evaluation.
* Evaluate patient-reported adverse events associated with Manuka honey using the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

OUTLINE: This is a multicenter study. Patients are stratified according to the percentage of esophagus in the radiation field (V60 \< 30% vs V60 ≥ 30%). Patients are randomized to 1 of 3 treatment arms.

* Arm I: Patients receive standard supportive care for esophagitis-related pain as needed during chemoradiotherapy.
* Arm II: Patients swallow liquid Manuka honey slowly over 3-5 minutes. Patients must refrain from eating and drinking for 1 hour after administration. Treatment continues 4 times per day during chemoradiotherapy.
* Arm III: Patients place Manuka honey lozenges in their mouth one at a time and swallow the honey as it dissolves (no chewing or swallowing it whole). Patients must refrain from eating and drinking for 1 hour after administration. Treatment continues 4 times per day during chemoradiotherapy.

Patients complete quality of life, pain swallowing diary, and pain assessments (Numerical Rating Pain Scale, EORTC QLQ-30 and Pain Subscale, and PRO-CTCAE) periodically during study treatment.

Patients are followed up at 12 weeks from the start of study treatment.

Manuka Honey in Preventing Esophagitis-Related Pain in Patients Receiving Chemotherapy and Radiation Therapy For Lung Cancer

Phase II Randomized Trial of Prophylactic Manuka Honey for the Reduction of Chemoradiation Therapy Induced Esophagitis-Related Pain During the Treatment of Lung Cancer

Esophagitis-related pain was measured using patient-reported pain on swallowing as assessed by the Numerical Rating Pain Scale (NRPS), an 11-point scale (0-10) in which 0 indicates no pain and 10 indicates the worst pain imaginable. Generally, scores of 1-4 indicate mild pain, scores of 5-6 indicate moderate pain, and scores of 7-10 indicate severe pain. Change was calculated by subtracting the baseline value from the 4-week value. The experimental arms (honey) were compared to the standard arm (supportive care).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study Evaluating a Proprietary Amino Acid Mixture (Enterade®) in Patients Receiving High-Dose Melphalan Conditioning Followed by Autologous Stem Cell Transplantation for Multiple Myeloma and Non-Hodgkin Lymphoma	NCT02919670	Multiple Myelom... Non-Hodgkin's L...	Enterade Placebo Standard Suppor...	18 Years -	Dana-Farber Cancer Institute
A Pilot Study of Structured Palliative Care for Patients Enrolled on Phase I Clinical Trials	NCT02543541	Cancer	Structured pall... Standard suppor...	18 Years -	Case Comprehensive Cancer Center
OptiTrain - Optimal Training Women With Breast Cancer	NCT02522260	Well Being	Resistance and ... Aerobic trainin... Standard suppor...	18 Years - 70 Years	Karolinska Institutet
Supervised Physical Activity in Young Women With Early Breast Cancer During Neoadjuvant Chemotherpy	NCT06190600	Breast Cancer	High Intensity ... neoadjuvant tre... Standard Suppor...	18 Years - 40 Years	The Greater Poland Cancer Centre
Manuka Honey in Preventing Esophagitis-Related Pain in Patients Receiving Chemotherapy and Radiation Therapy For Lung Cancer	NCT01262560	Dysphagia Lung Cancer Pain Esophagitis	Manuka honey in... Manuka honey in... Standard suppor...	18 Years -	Radiation Therapy Oncology Group
A Study Evaluating a Proprietary Amino Acid Mixture (Enterade®) in Patients Receiving High-Dose Melphalan Conditioning Followed by Autologous Stem Cell Transplantation for Multiple Myeloma and Non-Hodgkin Lymphoma	NCT02919670	Multiple Myelom... Non-Hodgkin's L...	Enterade Placebo Standard Suppor...	18 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for standard supportive care