Neoplasms

Skin and Connective Tissue Diseases

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Breast Neoplasms

Breast Diseases

Skin Diseases

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All Drugs and Chemicals

Herbal and Botanical

Omega 3 Fatty Acid

Soy Bean

Participants will take 11 capsules per day containing DHA-enriched triglyceride oil (1 g capsules containing at least 400 mg DHA) for a total of 5 g DHA/day divided into three times daily with meals or as tolerated.

Participants will take 11 capsules per day containing corn/soy oil blend capsules divided into three times daily with meals or as tolerated.

Participants will take 11 capsules of DHA oil for 12-18 weeks (84-126 days), beginning on day 1 of initial cycle of chemotherapy, and continuing for 4-6 cycles of chemotherapy prior to definitive breast surgery. Study will end when subject undergoes breast surgery.

Docosahexaenoic acid (DHA)

Participants will take 11 capsules of placebo (corn/soy oil blend) for 12-18 weeks (84-126 days), beginning on day 1 of initial cycle of chemotherapy, and continuing for 4-6 cycles of chemotherapy prior to definitive breast surgery. Study will end when subject undergoes breast surgery.

Placebo oral capsule

Deborah Miede, RN

John Mackey, MD

Docosahexaenoic acid (DHA) is an omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA). N-3 LCPUFA are essential fatty acids in the diet. The majority of n-3 LCPUFA in the diet is alpha-linolenic acid (ALA). While DHA can be synthesized from ALA and other n-3 LCPUFA in the body, endogenous synthesis is low. Consequently, the only way to significantly increase levels of DHA in tissues is by directly consuming this fatty acid. Common sources of DHA are fatty fish, fish oil and omega-3 supplements and fortified foods.

DHA is readily incorporated into membrane phospholipids and induces changes in the properties of the cell membrane including altered fluidity; permeability and membrane transport as well as activity of membrane bound receptors and enzymes.

It is well established that changes in membrane DHA has multiple effects in the body, including modulation of neurological, immune, and cardiovascular functions. In breast cancer, DHA increases sensitivity of breast cancer cells to different chemotherapeutic agents, and in animal models of breast cancer, dietary DHA decreases tumour growth. The investigator's preclinical studies demonstrate that DHA increases efficacy of both doxorubicin and docetaxel, two agents commonly used in the adjuvant setting for breast cancer treatment. Furthermore, DHA mitigates chemotherapy induced weight loss in mice, and reduces paclitaxel toxicities in breast cancer patients, strongly indicating that DHA protects against toxicity in normal tissues. Directly relevant to this study, increased DHA in breast adipose tissue correlates with improved response to chemotherapy, and increased dietary intake of n-3 LCPUFA, including DHA, results in increased DHA incorporation in breast adipose tissue. Lastly, in advanced metastatic breast cancer, DHA supplementation correlated with improved outcomes in a subset of patients. Consequently, the Investigators hypothesize that the therapeutic index (efficacy: toxicity ratio) will be improved with the addition of DHA. In this clinical trial, the Investigators will explore the benefit of DHA supplementation in combination with neoadjuvant chemotherapy in patients with early breast cancer.

RESEARCH QUESTION \& OBJECTIVES: The Investigators propose to evaluate incorporation of DHA in women with breast cancer in treatment naïve patients in combination with chemotherapy, and assess potential benefit of DHA supplementation in breast cancer patients, using change in Ki67 labeling index (marker of proliferation) as a marker of efficacy. This study will further investigate the relationship between DHA in plasma phospholipids (as a potential biomarker of tumour incorporation) and effect on systemic immune function.

METHODS: Patients directed to receive chemotherapy will receive capsules, each containing a minimum of 400 mg of DHA in the form of DHA enriched triglyceride oil or placebo (corn/soy oil blend) to be taken orally (11 capsules/day, throughout day as preferred by participant) for a total of 5 g DHA or placebo, for 12-18 weeks (84-126 days) beginning at the start of the first cycle of chemotherapy, and continued throughout 4-6 cycles of chemotherapy (3 weeks/ cycle). DHA will be discontinued 21 days after the last administration of cytotoxic chemotherapy. Tumour biopsies at baseline and post surgical removal will be assessed for Ki67 status as well as for markers of apoptosis and stem cell presence (by immunohistochemistry). Blood samples taken at baseline prior to each round of chemotherapy will be assessed for immune markers and plasma phospholipid content.

Docosahexaenoic Acid (DHA) for Women With Breast Cancer in the Neoadjuvant Setting

The Cross Cancer Institute and the University of Alberta encourages and supports the responsible and ethical sharing of data from clinical trials. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov.

Ki67 will be measured by image analysis at baseline biopsy and at experimental end (surgical excision).

Changes in level of DHA incorporation in plasma phospholipids will be assessed to identify the range of DHA incorporation in this patient population. Fatty acid composition of plasma phospholipids will be measured after lipid extraction, phospholipid separation on thin layer chromatography followed by methylation and separation identification by gas-liquid chromatography.

Systemic immune function will be assessed on stored plasma by U-PLEX Biomarker Group 1 electrochemiluminescent multiplex assays (MesoScale Discovery).

If incorporation of DHA in plasma phospholipids is variable within the DHA treatment arm, possible factors that may influence incorporation (e.g. age of participants) will be explored between high and low incorporators.

Breast tissue from participants receiving DHA or placebo will be assessed for markers of apoptosis (e.g. caspase-3) by immunohistochemistry and calculated by image analysis.

Pathological complete response in resected breast tissue and all sampled axillary nodes will be assessed as absence of invasive cancer on haematoxylin and eosin evaluation as per standard of care.

Rate of chemotherapy associated grade 3 and 4 toxicities, and chemotherapy- associated hospitalizations will be compared between DHA and placebo arms.

Canadian Institutes of Health Research (CIHR)

University of Alberta

AHS Cancer Control Alberta

Blood and Lymph Conditions

Immune System Diseases

Nutritional and Metabolic Diseases

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Malnutrition

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Nutrition Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

This group will be receive the DHA supplement

Children will be received either fish oil capsules (DHA group) or placebo capsules (placebo group) which is visually indistinguishable from DHA capsules (softgel). Each child will be receiving 100 mg/kg/day or placebo capsules without docosahexaenoic acid, during the first three months of treatment.

Placebo

Maria de Lourdes Barbosa-Cortes, MSc

The purpose of this study is to evaluate if enteral docosahexaenoic acid (DHA) administration during the first three months of treatment reduces the deterioration of nutritional status, treatment toxicity and early mortality in children with acute lymphoblastic leukemia.

Cancer is often associated with malnutrition.The most of children with cancer loss weight, and 50-80% of patients with cancer experience morbidity and mortality as a result of progressive wasting.

As a consequence of malnutrition, patients with cancer may have a poorer outcome, reduced effectiveness of chemotherapy and increased risk of chemotherapy-induced toxicity compared to those who are well nourished at diagnosis. On the other hand, in the recent years, there has been increased focus on the role of long chain polyunsaturated fatty acids and their effect on prevention and treatment of several diseases. The results of animal studies and adults with cancer have demonstrated that the consumption of long chain polyunsaturated fatty acids can slow the growth of cancer, increase the efficacy of chemotherapy and reduce loss weight and the side effects of the chemotherapy.

Beneficial effects of enteral long chain polyunsaturated fatty acids has been reported in adults with cancer. However, in children with cancer the scientific reports are scarce; therefore, is necessary to evaluate if the long chain polyunsaturated fatty acids administration in children with acute lymphoblastic leukemia has the same effects on clinical and nutritional outcomes that have been previously showed by different studies in adults with cancer.

Effect of Enteral Docosahexaenoic Acid Administration in Children With Acute Lymphoblastic Leukemia

The Effect of Enteral Administration of Polyunsaturated Omega-3 Fatty Acids on Nutritional Status; the Treatment Toxicity and Early Mortality in Children With Acute Lymphoblastic Leukemia - a Controlled Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Docosahexaenoic Acid (DHA) for Women With Breast Cancer in the Neoadjuvant Setting	NCT03831178	Breast Cancer	Docosahexaenoic... Placebo oral ca...	18 Years -	AHS Cancer Control Alberta
Effect of Enteral Docosahexaenoic Acid Administration in Children With Acute Lymphoblastic Leukemia	NCT01051154	Acute Lymphobla... Malnutrition	Docosahexaenoic... Placebo	4 Years - 15 Years	Coordinación de Investigación en Salud, Mexico

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