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

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

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).

Study Overview

• Status: Terminated
• Conditions: Metastatic Breast Cancer; Estrogen Receptor Positive Tumor; Progesterone Receptor Positive Tumor; HER-2 Negative Tumor
• Intervention / Treatment: Dietary supplement: Dietary supplementation with vegetable oil; Dietary supplement: Dietary supplementation with fish oil.

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Angers, France, 49933
    • Institut de Cancérologie de l'Ouest (ICO)
  • Bourges, France, 18016
    • Centre Hospitalier Jacques Coeur
  • Brest, France, 29609
    • CHU Morvan
  • Caen, France, 14076
    • Centre Francois Baclesse
  • Cholet, France, 49325
    • Centre hospitalier
  • La Roche Sur Yon, France, 85925
    • Centre Hospitalier Departemental Les Oudairies
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Lorient, France, 56100
    • Centre Hospitalier Bretagne Sud
  • St Doulchard, France, 18230
    • Clinique Guillaume De Varye
  • St Grégoire, France, 35768
    • Centre Hospitalier Prive
  • Tours, France, 37044
    • Chu Bretonneau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: DHA-free arm; Dietary supplementation with vegetable oil.	Dietary supplement: Dietary supplementation with vegetable oil; Patients randomized in this arm will take 3 cans/day with vegetable oil : no DHA no EPA.
EXPERIMENTAL: DHA arm; Dietary supplementation with fish oil.	Dietary supplement: Dietary supplementation with fish oil.; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Tours
• Collaborators: Institut Cancerologie de l'Ouest
• Investigators: Principal Investigator: Philippe Bougnoux, MD, PhD, University Hospital, Tours

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (ACTUAL): June 1, 2014
• Study Completion (ACTUAL): June 1, 2014

Study Registration Dates

• First Submitted: February 27, 2012
• First Submitted That Met QC Criteria: March 5, 2012
• First Posted (ESTIMATE): March 8, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): July 29, 2015
• Last Update Submitted That Met QC Criteria: July 28, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: DHA; Metastatic Breast Cancer; Dietary supplementation; PUFA; First-Line chemotherapy; Taxane or Anthracycline; First-Line Taxane or Anthracycline based chemotherapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: PHRN11-PB; 2011-A01029-32 (OTHER: French Health Products Safety Agency)