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Diet Restriction and Exercise-induced Adaptations in Metastatic Breast Cancer (DREAM)

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ClinicalTrials.gov Identifier: NCT03795493
Recruitment Status : Enrolling by invitation
First Posted : January 7, 2019
Last Update Posted : May 11, 2021
Sponsor:
Collaborators:
Canadian Cancer Society (CCS)
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Carla Prado, University of Alberta

Tracking Information
First Submitted Date  ICMJE November 26, 2018
First Posted Date  ICMJE January 7, 2019
Last Update Posted Date May 11, 2021
Actual Study Start Date  ICMJE April 23, 2019
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 7, 2021)
Tumor size change after 6 cycles (mm) [ Time Frame: 0-6 weeks before the first chemotherapy treatment of the first cycle and 1-4 weeks after the last chemotherapy treatment of the last cycle ]
Change in tumor size measured by computerized tomography after 6 cycles.
Original Primary Outcome Measures  ICMJE
 (submitted: January 4, 2019)
Tumor size [ Time Frame: 0-6 weeks before the first chemotherapy treatment and 1-4 weeks after the last chemotherapy treatment ]
Percent change in tumor size measured by computerized tomography.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 7, 2021)
  • Tumor response to therapy by magnetic resonance imaging (mm²/s) [ Time Frame: 0-2 weeks before the first chemotherapy treatment of the first cycle and 2-3 weeks after the last chemotherapy treatment of the last cycle ]
    Magnetic resonance imaging (MRI) derived water apparent diffusion coefficient within the tumor
  • Tumor size change after 3 cycles (mm) [ Time Frame: 0-6 weeks before the first chemotherapy treatment of the first cycle and 1-3 weeks after the last chemotherapy treatment of the third cycle ]
    Change in tumor size measured by computerized tomography after 3 cycles.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 4, 2019)
  • Tumor response to therapy by magnetic resonance imaging [ Time Frame: 0-6 weeks before the first chemotherapy treatment and 1-4 weeks after the last chemotherapy treatment ]
    Magnetic resonance imaging (MRI) derived water apparent diffusion coefficient within the tumor
  • Tumor response to therapy by circulating blood biomarkers [ Time Frame: 0-6 weeks before the first chemotherapy treatment and 1-4 weeks after the last chemotherapy treatment ]
    Circulating blood cancer antigen 27.29 (CA 27.29)
Current Other Pre-specified Outcome Measures
 (submitted: May 7, 2021)
  • Left ventricular ejection fraction (%) [ Time Frame: 0-2 weeks before the first chemotherapy treatment of the first cycle and 2-3 weeks after the last chemotherapy treatment of the last cycle ]
    MRI-derived left ventricular ejection fraction
  • Left ventricular global longitudinal strain (%) [ Time Frame: 0-2 weeks before the first chemotherapy treatment of the first cycle and 2-3 weeks after the last chemotherapy treatment of the last cycle ]
    MRI-derived left ventricular global longitudinal strain
  • Left ventricular mass (g/m²) [ Time Frame: 0-2 weeks before the first chemotherapy treatment of the first cycle and 2-3 weeks after the last chemotherapy treatment of the last cycle ]
    MRI-derived left ventricular mass
  • Liver fat fraction (%) [ Time Frame: 0-2 weeks before the first chemotherapy treatment of the first cycle and 2-3 weeks after the last chemotherapy treatment of the last cycle ]
    Percent of fat in liver derived by PROFIT1 chemical-shift encoded MRI
  • Liver T1 relaxation time (ms) [ Time Frame: 0-2 weeks before the first chemotherapy treatment of the first cycle and 2-3 weeks after the last chemotherapy treatment of the last cycle ]
    MRI-derived relaxation time from healthy liver
  • Thigh skeletal muscle T1 relaxation time (ms) [ Time Frame: 0-2 weeks before the first chemotherapy treatment of the first cycle and 2-3 weeks after the last chemotherapy treatment of the last cycle ]
    MRI-derived skeletal muscle T1 relaxation time at mid-thigh
  • Thigh muscle volume (mL) [ Time Frame: 0-2 weeks before the first chemotherapy treatment of the first cycle and 2-3 weeks after the last chemotherapy treatment of the last cycle ]
    PROFIT1 chemical-shift encoded MRI of the mid-thigh will be used to assess thigh muscle volume
  • Thigh skeletal muscle fat fraction % [ Time Frame: 0-2 weeks before the first chemotherapy treatment of the first cycle and 2-3 weeks after the last chemotherapy treatment of the last cycle ]
    Percent of intermuscular fat in thigh muscle derived by PROFIT1 chemical-shift encoded MRI
  • Patient-reported treatment symptoms [ Time Frame: 0-2 weeks before the first chemotherapy treatment of the first cycle, at each chemotherapy treatment, and 2-3 weeks after the last chemotherapy treatment of the last cycle ]
    Patient-reported treatment symptoms assessed using the Rotterdam Symptom Checklist
  • Self reported quality of life [ Time Frame: 0-2 weeks before the first chemotherapy treatment of the first cycle, at the first chemotherapy treatment of 4th cycle, and 2-3 weeks after the last chemotherapy treatment of the last cycle ]
    Quality of life assessed using the total score from the Functional Assessment of Cancer Therapy - Fatigue Questionnaire. Scores can range from 0 - 52 where a high score represents a better quality of life.
  • Fatigue [ Time Frame: 0-2 weeks before the first chemotherapy treatment of the first cycle, at the first chemotherapy treatment of 4th cycle, and 2-3 weeks after the last chemotherapy treatment of the last cycle ]
    Fatigue assessed using the total score from the Functional Assessment of Cancer Therapy - Fatigue Questionnaire. Scores can range from 0 - 52 where a high score represents a lower level of fatigue.
  • Progression-free survival (months) [ Time Frame: Two years after study enrollment ]
    Progression-free survival time extracted from Cancer Control Alberta's electronic database
  • Overall survival (months) [ Time Frame: Two years after study enrollment ]
    Overall survival time extracted from Cancer Control Alberta's electronic database
Original Other Pre-specified Outcome Measures
 (submitted: January 4, 2019)
  • Patient-reported treatment symptoms [ Time Frame: 0-6 weeks before the first chemotherapy treatment, at the mid-point of study participation, and 1-4 weeks after the last chemotherapy treatment ]
    Patient-reported treatment symptoms assessed using the Rotterdam Symptom Checklist
  • Self reported quality of life [ Time Frame: 0-6 weeks before the first chemotherapy treatment, at the mid-point of study participation, and 1-4 weeks after the last chemotherapy treatment ]
    Quality of life assessed using the total score from the Functional Assessment of Cancer Therapy - Fatigue Questionnaire. Scores can range from 0 - 52 where a high score represents a better quality of life.
  • Progression-free survival [ Time Frame: Two years after study enrollment ]
    Average survival time extracted from Cancer Control Alberta's electronic database
  • Overall survival [ Time Frame: Two years after study enrollment ]
    Average survival time extracted from Cancer Control Alberta's electronic database
 
Descriptive Information
Brief Title  ICMJE Diet Restriction and Exercise-induced Adaptations in Metastatic Breast Cancer
Official Title  ICMJE Diet Restriction and Exercise-induced Adaptations in Metastatic Breast Cancer
Brief Summary Fifty patients with metastatic breast cancer will be randomly assigned to an acute intervention consisting of both aerobic exercise and caloric restriction administered acutely prior to each of six chemotherapy cycles, or to usual care. The aerobic exercise intervention will consist of a single supervised recumbent cycle ergometer session performed concurrent to each chemotherapy infusion. The diet intervention consists of provision of meals freshly prepared in a metabolic kitchen with caloric content equivalent to 50% of measured energy requirements and low carbohydrate content for 48-72 hours prior to each chemotherapy infusion. Tumor outcomes will be assessed via CT scan (tumor size) and MRI (novel marker of tumor regression), while treatment side effects will be assessed by MRI and treatment symptoms and quality of life will be assessed via questionnaire before, during and after up to six chemotherapy cycles of a consistent treatment protocol. Progression-free and overall survival will be tracked for two years after diagnosis.
Detailed Description

Despite major advances in recent decades in treatment for early stage breast cancer leading to an 89% 5-year survival rate, metastatic breast cancer is still considered incurable due to resistance to most available treatments. As such, 5-year survival rate for metastatic breast cancer is only 22%. One mechanism for resistance to cancer therapies and promotion of metastasis in solid tumors is that their vascular system is impaired causing diminished delivery of systemic therapy and oxygen. Furthermore, toxicity can be quite high with metastatic regimens, which can limit the dose received. Both diet and exercise have been used to attenuate treatment toxicity, but the promising preclinical evidence showing their potential to enhance chemotherapy efficacy and survival has not been studied in humans. For example, a single bout of aerobic exercise substantially increased tumor blood flow and oxygen delivery, suggesting that chemotherapy delivery to the tumor would be enhanced. Short periods of fasting or caloric restriction also appear to be safe and effective strategies to inhibit tumor growth and enhance chemotherapy efficacy, while also promoting resistance to chemotherapy in healthy cells. Furthermore, combining aerobic exercise and caloric restriction can elicit synergistic effects on outcomes relevant to cancer, including body composition, aerobic fitness, fasting insulin and glucose, insulin-like growth factor, and tumor promoter pathways.

Study Design: With preclinical proof-of-principle and clinical safety and feasibility of each intervention independently established, this study will be a phase II, two-arm, single blind, randomized controlled trial. Fifty patients will be randomly assigned to an acute intervention consisting of both caloric restriction administered acutely prior to and aerobic exercise during each treatment of six chemotherapy cycles, or to usual care.

Approach: Participants will include adults with metastatic breast cancer with measurable metastases that will receive intravenous chemotherapy. The aerobic exercise intervention will consist of a single supervised recumbent cycle ergometer session performed concurrent to each chemotherapy infusion. The diet intervention consists of provision of meals freshly prepared in a metabolic kitchen with caloric content equivalent to 50% of measured energy requirements and low carbohydrate content for 48-72 hours prior to each chemotherapy infusion. The diet period will be reduced from 72 to 48 hours when there are <7 days between infusions (ie weekly protocols) to avoid inducing a sustained caloric deficit leading to weight loss. This acute intervention does not lead to long-term nutritional imbalances. Exercise intensity and meals will be individualized to participant abilities and preferences. All participants, regardless of group assignment, will receive a one-time phone consultation with a registered dietitian and a certified exercise physiologist to enhance recruitment and retention. Tumor outcomes will be assessed via CT scan (tumor size) and MRI (novel marker of tumor regression), while treatment side effects will be assessed by MRI and treatment symptoms and quality of life will be assessed via questionnaire before, during and after up to six chemotherapy cycles of a consistent treatment protocol. Progression-free and overall survival will be tracked for two years after diagnosis.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Supportive Care
Condition  ICMJE Breast Cancer
Intervention  ICMJE Behavioral: Short-term diet and exercise intervention
Participants assigned to the intervention group will perform both the diet and acute exercise interventions. The interventions will be applied prior to up to six chemotherapy cycles of a consistent protocol. The total number of treatments of a given protocol received prior to treatment conclusion is dependent on patient condition and oncologic care preferences.
Study Arms  ICMJE
  • Experimental: Intervention Group
    Standard chemotherapy treatment and oncology care plus short-term diet and exercise intervention.
    Intervention: Behavioral: Short-term diet and exercise intervention
  • No Intervention: Control Group
    Standard chemotherapy treatment and oncology care.
Publications * Kirkham AA, King K, Joy AA, Pelletier AB, Mackey JR, Young K, Zhu X, Meza-Junco J, Basi SK, Hiller JP, Brkin T, Michalowski B, Pituskin E, Paterson DI, Courneya KS, Thompson RB, Prado CM. Rationale and design of the Diet Restriction and Exercise-induced Adaptations in Metastatic breast cancer (DREAM) study: a 2-arm, parallel-group, phase II, randomized control trial of a short-term, calorie-restricted, and ketogenic diet plus exercise during intravenous chemotherapy versus usual care. BMC Cancer. 2021 Oct 10;21(1):1093. doi: 10.1186/s12885-021-08808-2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Enrolling by invitation
Estimated Enrollment  ICMJE
 (submitted: September 4, 2019)
50
Original Estimated Enrollment  ICMJE
 (submitted: January 4, 2019)
40
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of stage IV or metastatic breast cancer;
  • Measurable metastases.
  • Age >18
  • Starting (or having only received one treatment of) any type of intravenously administered chemotherapy;
  • Eastern Cooperative Oncology Group (ECOG) Score < 3
  • Oncologist approval to participate
  • Able to communicate and read and understand English;
  • Willing and able to adhere to the study interventions and assessments;

Exclusion Criteria:

  • Limitations to sustained exercise (including bone metastases in the femur neck);
  • Clinical evidence of cachexia (oncologist's discretion, study team will use body mass index <18.5kg/m² as a flag to highlight concern to treating oncologist);
  • Body mass >109 kg at time of enrollment;
  • Diabetes;
  • Severe food allergies;
  • History of eating disorder (diagnosed or self-reported);
  • Strict diet restrictions including vegetarian or vegan;
  • Unable to provide informed consent (i.e. cognitive impairment);
  • Supplemental oxygen requirement;
  • Uncontrolled pleural effusions (oncologists approval if pleural effusions exists and are controlled);
  • Bilirubin >30 umol/L;
  • Creatinine >120 umol/L;
  • Pregnant;
  • Contraindications to 3T MRI for research purposes
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03795493
Other Study ID Numbers  ICMJE HREBA.CC-18-0657
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Carla Prado, University of Alberta
Study Sponsor  ICMJE University of Alberta
Collaborators  ICMJE
  • Canadian Cancer Society (CCS)
  • Canadian Institutes of Health Research (CIHR)
Investigators  ICMJE
Principal Investigator: Carla Prado, PhD University of Alberta
Principal Investigator: Richard Thompson, PhD University of Alberta
PRS Account University of Alberta
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP