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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 : September 6, 2019
Sponsor:
Collaborators:
Canadian Cancer Society Research Institute (CCSRI)
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Carla Prado, University of Alberta

Brief Summary:
Fifty adult women 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 treatments, 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 under the supervision of a dietitian with caloric content equivalent to 50% of measured energy requirements and low carbohydrate content for the 72 hours prior to each chemotherapy. 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 treatments of a consistent treatment protocol. Progression-free and overall survival will be tracked for two years after diagnosis.

Condition or disease Intervention/treatment Phase
Breast Cancer Behavioral: Short-term diet and exercise intervention Not Applicable

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, 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 aerobic exercise and caloric restriction administered acutely prior to each of six chemotherapy treatments, or to usual care.

Approach: Participants will include adult women with metastatic breast cancer with measurable pulmonary, visceral, liver, or lymphatic 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 under the supervision of a dietitian with caloric content equivalent to 50% of measured energy requirements and low carbohydrate content for the 72 hours prior to each chemotherapy. This acute intervention does not lead to long-term nutritional imbalances or weight loss. Exercise intensity and meals will be individualized to participant abilities and preferences. Tumor outcomes will be assessed via CT scan (tumor size) and MRI (novel marker of tumor regression), while symptoms and quality of life will be assessed via questionnaire before, during and after up to six chemotherapy treatments of a consistent treatment protocol. Progression-free and overall survival will be tracked for two years after diagnosis.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Diet Restriction and Exercise-induced Adaptations in Metastatic Breast Cancer
Actual Study Start Date : April 23, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Intervention Group
Standard chemotherapy treatment and oncology care plus short-term diet and exercise intervention.
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 treatments 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.

No Intervention: Control Group
Standard chemotherapy treatment and oncology care.



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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


Other Outcome Measures:
  1. Patient-reported treatment symptoms [ Time Frame: 0-6 weeks before the first chemotherapy treatment, 2-4 weeks after the third chemotherapy, and 2-4 weeks after six chemotherapy treatments ]
    Patient-reported treatment symptoms assessed using the Rotterdam Symptom Checklist

  2. Self reported quality of life [ Time Frame: 0-6 weeks before the first chemotherapy treatment, 2-4 weeks after the third chemotherapy, and 2-4 weeks after six chemotherapy treatments ]
    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.

  3. Progression-free survival [ Time Frame: Two years after study enrollment ]
    Average survival time extracted from Cancer Control Alberta's electronic database

  4. Overall survival [ Time Frame: Two years after study enrollment ]
    Average survival time extracted from Cancer Control Alberta's electronic database

  5. Liver T1 relaxation time [ Time Frame: 0-6 weeks before the first chemotherapy treatment and 1-4 weeks after the last chemotherapy treatment ]
    MRI-derived relaxation time from healthy liver

  6. Left ventricular ejection fraction [ Time Frame: 0-6 weeks before the first chemotherapy treatment and 1-4 weeks after the last chemotherapy treatment ]
    MRI-derived left ventricular ejection fraction

  7. Thigh muscle mass [ Time Frame: 0-6 weeks before the first chemotherapy treatment and 1-4 weeks after the last chemotherapy treatment ]
    Dixon fat water separation by MRI of the mid-thigh

  8. Thigh muscle quality [ Time Frame: 0-6 weeks before the first chemotherapy treatment and 1-4 weeks after the last chemotherapy treatment ]
    Percent of intermuscular fat in thigh muscle derived by Dixon fat water separation imaging

  9. Thigh skeletal muscle T1 relaxation time [ Time Frame: 0-6 weeks before the first chemotherapy treatment and 1-4 weeks after the last chemotherapy treatment ]
    MRI-derived skeletal muscle T1 relaxation time at mid-thigh



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women
  • Diagnosis of stage IV or metastatic breast cancer;
  • Measurable pulmonary, visceral, liver, or lymphatic metastases.
  • Age >18
  • Starting any type of first or second line 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:

  • Chemotherapy delivered weekly;
  • Limitations to sustained exercise (including bone metastases in the femur neck);
  • Body mass index <18.5 kg/m2;
  • Body mass >109 kg at time of enrollment;
  • Diabetes;
  • Severe food allergies;
  • History of eating disorder (diagnosed or self-reported);
  • 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 >1.5 mg/dL;
  • Creatinine >1.0 mg/dL;
  • Pregnant;
  • Contraindications to 3T MRI for research purposes

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03795493


Locations
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Canada, Alberta
University of Alberta
Edmonton, Alberta, Canada, T6G 2E1
Sponsors and Collaborators
University of Alberta
Canadian Cancer Society Research Institute (CCSRI)
Canadian Institutes of Health Research (CIHR)
Investigators
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Principal Investigator: Carla Prado, PhD University of Alberta
Principal Investigator: Richard Thompson, PhD University of Alberta

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Responsible Party: Carla Prado, Associate Professor, University of Alberta
ClinicalTrials.gov Identifier: NCT03795493     History of Changes
Other Study ID Numbers: HREBA.CC-18-0657
First Posted: January 7, 2019    Key Record Dates
Last Update Posted: September 6, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Carla Prado, University of Alberta:
Exercise
Nutrition
Caloric Restriction
Chemotherapy
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases