A Randomised Study of Docosahexaenoic Acid (DHA) in Metastatic Breast Cancer

Study Overview
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Brief Summary
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The aim of this study is to increase, by DHA-induced chemosensitization, the activity of anticancer chemotherapy in patients with a metastatic advanced breast cancer, by a nutritional approach with marin-derived PolyUnsaturated Fatty Acids (PUFA).

Detailed Description
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Local relapses and metastases make breast cancer a deadly disease. A major goal remains the improvement of treatment efficacy, meaning increasing toxicity to tumor tissue, without additional toxicity to non-tumor tissues. The literature indicates that DHA sensitizes breast malignant tumors, but not non-tumor tissues, to chemotherapy and to radiotherapy through a variety of mechanisms. DHA enrichment of tissues can be achieved through a dietary supplementation of DHA-containing oils, such as fish oil, both in experimental animal models or in humans. Therefore, this represents an original nutritional approach to increase the activity of anticancer treatments through an enhanced specificity toward tumor tissues.

Official Title
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A Phase III Randomized, Multicenter, Two Arms Double-blind Trial Versus Placebo, Evaluating the Interest of a Dietary Supplementation With Docosahexaenoic Acid (DHA) During Chemotherapy for Metastatic Breast Cancer

Conditions
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Metastatic Breast Cancer, Progesterone Receptor Positive Tumor, Estrogen Receptor Positive Tumor, HER-2 Negative Tumor

Intervention / Treatment
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* Dietary Supplement: Dietary supplementation with fish oil.
* Dietary Supplement: Dietary supplementation with vegetable oil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic breast cancer requiring first-line taxanes or anthracyclines based chemotherapy HER2 negative, HR positive Life expectancy > 3 months ECOG Performance Status < or = 2 within 15 days before randomization Measurable and/or evaluable disease according to RECIST criteria 1.1 Age > or = 18 years and < or = 80 years Body Mass Index (BMI)>17 for patients < 70 years and BMI>21 for patients > 70 years, within 15 days before randomization Hepatic parameters : total bilirubin strictly normal, AST and ALT < or = 3xULN (5 if liver metastases) within 15 days before randomization Signed written informed consent Exclusion Criteria: Triple negative breast cancer or HER2 over expression Symptomatic central nervous system metastases Previous chemotherapy for metastatic breast cancer Obesity with BMI > 35 within 15 days before randomization Presence of another invasive cancer Uncontrolled Cardiac disease or uncontrolled hypertension Milk protein intolerance Known food allergy to fish Women of childbearing potential not using adequate contraceptive measures, pregnant or breast feeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: DHA-free arm<br>Dietary supplementation with vegetable oil. | Dietary Supplement: Dietary supplementation with vegetable oil<br>* Patients randomized in this arm will take 3 cans/day with vegetable oil : no DHA no EPA.<br>|
| Experimental: DHA arm<br>Dietary supplementation with fish oil. | Dietary Supplement: Dietary supplementation with fish oil.<br>* Patients randomized in this arm will take 3 cans/day with fish oil : DHA is 1.56 g/d and EPA is 2.64 g/d.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS is defined as time from randomization to disease progression or death. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR will be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). | The objective response is the best objective response observed from the start of treatment to progression. | 
| Overall Survival (OS) | OS is defined as time from randomization to death due to any cause. | 3 years after last chemotherapy in study | 
| Time To Progression (TTP) | TTP is defined as time from randomization to first documentation of objective tumor progression according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). | First progression | 
| Safety ans tolerance of dietary supplementation/chemotherapy association | Incidence and severity of adverse events will be assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. | 4 months | 
| Dietary supplementation compliance | Compliance will be assessed through patient's diary. | 4 months | 
| Quality Of Life (QOL) | QOL will be assessed by QLQ-C30 and BR23 questionnaires. | At C1, after 4 months of chemotherapy, and at the end of chemotherapy. | 
| Pain evaluation | Pain will be assessed by a Visual Analog Scale (VAS) and analgesic consumption. | 4 months | 
| DHA plasma level | Plasma phospholipids DHA incorporation will be measured with a blood sample. | Before dietary supplementation (at C1), and after 4 months of dietary supplementation. | 
| Neuropathy evaluation | Neuropathy will be assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Breast Cancer, First-Line chemotherapy, Taxane or Anthracycline, DHA, PUFA, Dietary supplementation, First-Line Taxane or Anthracycline based chemotherapy