IH636 Grape Seed Extract in Preventing Breast Cancer in Postmenopausal Women at Risk of Developing Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of IH636 grape seed extract may prevent breast cancer. PURPOSE: This phase I trial is studying the side effects and best dose of IH636 grape seed extract in preventing breast cancer in postmenopausal women at risk of developing breast cancer.

Detailed Description
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OBJECTIVES: Determine the efficacy of IH636 grape seed proanthocyanidin extract, in terms of suppression of estrogen biosynthesis, in healthy post-menopausal women at high risk of developing breast cancer. Determine the safety and tolerability of this dietary supplement, in terms of symptoms and changes in markers of bone and lipid metabolism and in markers of nonspecific adrenal suppression, in these participants. Determine, preliminarily, an optimum biologic dose of this dietary supplement, as defined by suppression of serum estradiol, in these participants. Determine a minimum duration of use of this dietary supplement to achieve aromatase inhibition in these participants. OUTLINE: This is a pilot, dose-finding, placebo-controlled study. Participants receive oral placebo once or twice daily on days -14 to 0. Participants then receive oral IH636 grape seed proanthocyanidin extract once or twice daily on days 1-85. Treatment continues in the absence of toxicity. Cohorts of 6 participants receive one of four dose levels of IH636 grape seed proanthocyanidin extract up to an established safe dose. PROJECTED ACCRUAL: A total of 24 participants will be accrued for this study within 12 months.

Official Title
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A Phase I Prevention Trial of ACTIVIN Grape Seed Extract as an Aromatase Inhibitor In Healthy Postmenopausal Women at Risk for Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Dietary Supplement: IH636 grape seed proanthocyanidin extract


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: At risk of developing breast cancer No history of breast cancer or ductal carcinoma in situ PATIENT CHARACTERISTICS: Age 40 to 75 Sex Female Menopausal status Postmenopausal, defined by 1 of the following criteria: No spontaneous menses for ≥ 12 months Prior bilateral oophorectomy Prior hysterectomy with follicle-stimulating hormone within menopausal range Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Hemoglobin ≥ 9.0 g/dL Platelet count ≥ 100,000/mm^3 WBC ≥ 3,500/mm^3 Absolute granulocyte count ≥ 1,500/mm^3 No coagulation disorders Hepatic SGOT and SGPT ≤ 2 times upper limit of normal (ULN) Bilirubin ≤ 1.5 times ULN Renal Creatinine ≤ 1.5 times ULN Cardiovascular No major illness of the cardiovascular system Pulmonary No major illness of the respiratory system Other No history of other invasive cancer within the past 5 years except squamous cell or basal cell skin cancer No major systemic infection No Cushing's syndrome or adrenal insufficiency No osteoporosis, defined as a bone mineral density T-score ≥ -2.5 on dual-energy x-ray absorptiometry scan (calcium and/or cholecalciferol [vitamin D] supplementation AND/OR bisphosphonate therapy allowed provided participant is on a stable dose during study participation) PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy More than 3 months since prior hormone-modifying medications, including any of the following: Oral contraceptives Hormone replacement therapy Selective estrogen receptor modifiers Aromatase inhibitors Gonadotropin-releasing hormone modifiers Concurrent dehydroepiandrosterone (DHEA) allowed, provided dose remains constant during study participation Radiotherapy Not specified Surgery Not specified Other No red wine, red grapes, or white button mushrooms directly before or during study treatment White and seedless grapes allowed No other concurrent therapy

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dietary Supplement: grape seed proanthocyanidin extract<br>Administered orally. | Dietary Supplement: IH636 grape seed proanthocyanidin extract<br>* Dose escalation as follows: 50 mg/day, 300 mg/day, 1000 mg/day, 2000 mg/day, 2800 mg/day, 4000 mg/day, 4800 mg/day and 6000 mg/day in separate patient groups for each dosage<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estrogen suppression as measured by serum estradiol, estrone, estrone sulfate, and sex hormone binding globulin |  | at 1, 2, 4, 8, and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Androgenic effects as measured by serum testosterone, androstenedione, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS) |  | at 1, 2, 4, 8, and 12 weeks | 
| Lipid effects as measured by total cholesterol, LDL, HDL, and triglycerides |  | at 12 weeks | 
| Bone metabolic effects as measured by bone-specific alkaline phosphatase and N-telopeptides |  | at 12 weeks | 
| Insulin regulatory effects as measured by insulin-like growth factor 1 (IGF1) and insulin-like growth factor-binding protein 3 (IGFBP3) |  | at 12 weeks | 
| Pharmacokinetics as measured by procyanidins |  | before and after first dose and then at 1, 2, 4, 8, and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer