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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Dietary supplement: IH636 grape seed proanthocyanidin extract

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dietary Supplement: grape seed proanthocyanidin extract; Administered orally.	Dietary supplement: IH636 grape seed proanthocyanidin extract; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: January 6, 2005
• First Submitted That Met QC Criteria: January 6, 2005
• First Posted (Estimate): January 7, 2005

Study Record Updates

• Last Update Posted (Estimate): June 8, 2015
• Last Update Submitted That Met QC Criteria: June 3, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Protective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antioxidants; Proanthocyanidin; Procyanidin
• Other Study ID Numbers: 03178; P30CA033572 (U.S. NIH Grant/Contract); CHNMC-IRB-03178; CDR0000407637 (Registry Identifier: NCI PDQ)