Flaxseed as Maintenance Therapy for Ovarian Cancer Patients in Remission

For the year 2014, it is projected there will be 21,980 women diagnosed and 14,270 deaths
from ovarian cancer (OC) in the US. OC is the leading cause of death from gynecologic
malignancies and ranks second among newly diagnosed gynecological cancers in the United
States. More than 70% of patients present with advanced disease (stages II-IV). Although most
patients (70-80%) initially respond to cytoreductive surgery and adjuvant paclitaxel and
platinum-based chemotherapy, approximately 80% of these women will experience disease
recurrence. For stages III and IV, the risk of recurrence is very high, with 5-year survival
rates ranging from just 13% to 44%. Furthermore, OC represents a high potential for
metastases even in the setting of complete response to initial therapy. Efforts to devise new
treatment strategies are therefore essential in order to improve survival. In this grant
application, the investigators postulate that utilizing dietary supplementation of flaxseed
for maintenance therapy in patients with OC in clinical remission following treatment with
platinum-based regimens will be tolerable and prolong their progression-free survival (PFS).
The investigators hypothesis is based on the following:

- Data from the investigators laboratory revealed that flaxseed effectively decreased
severity and progression of OC in the only spontaneous preclinical egg-laying hen model
that fully recapitulates human OC.

- In a phase II study, flaxseed supplementation reduced proliferation rates of prostate
cancer after just 30 days.

- Flaxseed has been shown to inhibit solid tumor growth and metastases in several other
preclinical cancer models (breast, prostate, colon).

- Flaxseed is a safe dietary supplement for cancer patients.

- Flaxseed supplementation increased survival in our investigators' animal model and these
flaxseed-fed hens exhibited lower inflammatory markers and maintained a healthy weight,
inferring a better quality of life (QOL).

Inclusion Criteria:

- Patients with a diagnosis of OC including epithelial ovarian carcinoma, primary
peritoneal cancer or fallopian tube cancer who are currently in clinical remission as
determined by the PI or co-I and are within 4 months of completion of cancer
treatment.

- Patients at risk of clinical relapse: patients of any stage who are in remission who
have undergone surgical debulking and adjuvant chemotherapy.

- Patients must have adequate:

- Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to
1,500/mcl, equivalent to Common Toxicity Criteria (CTCAE v4.0) Grade 1. Platelets
greater than or equal to 100,000/mcl (CTCAE v4.0 Grade 0-1). Hemoglobin (Hgb)
greater than or equal to 9.0g/dl (CTCAE v4.0 Grade 2).

- Renal function: Creatinine less than or equal to 1.5 x institutional upper limit
normal (ULN), CTCAE v4.0 Grade 1.

- Hepatic function: Bilirubin less than or equal to 1.5 x ULN (CTCAE v4.0 Grade 1).
Serum glutamate oxaloacetate transaminase (SGOT) and alkaline phosphatase ≤ 2.5 x
ULN (CTCAE v4.0 Grade 1).

- Women of childbearing potential must have a negative pregnancy test.

Exclusion Criteria:

- Patients with a history of other invasive malignancies, with the exception of
non-melanoma skin cancer, are excluded if there is any evidence of other malignancy
being present within the last five years. Patients are also excluded if their previous
cancer treatment contraindicates this protocol therapy.

- Patients with ovarian cancer of low malignant potential (borderline cancers).

- Patients who have received prior radiotherapy or chemotherapy for another malignancy.

- Patients who are pregnant or lactating.

- Patients with serious medical or psychiatric illness.

- Patients with a history of inflammatory bowel disease, problems with chronic diarrhea
or history of bowel obstruction.

- Patient has received other investigational drugs within 28 days before enrollment.

- Patients with concurrent uncontrolled illness.

- Patients unable to tolerate and/or allergies to flaxseed or flaxseed preparations.

- Patients with Gynecologic Oncology Group (GOG) performance status > 2.

- Patients with a history of uncontrolled diabetes (as flaxseed can lower blood glucose
levels and might have additive effects when used with anti-diabetic drugs).

- Patients concurrently using anticoagulants/antiplatelets on a DAILY BASIS, including
aspirin, Clopidogrel (Plavix), Ticlopidine (Ticlid), and Coumadin.

- Patients with a diagnosis of/problems with von Willebrand's disease or other bleeding
disorders (as flaxseed may slow blood clotting; the risk of bruising or bleeding in
people on anticoagulants or with bleeding disorders may be a concern).

- Flaxseed supplementation may be contraindicated in patients with acute abdomen,
esophageal stricture or perforation, dysphagia, GI obstruction or ileus, acute
intestinal inflammation or unexplained abdominal pain. Patients with any of these
conditions will be excluded from this trial as the high fiber content of flaxseed may
make these conditions worse