Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Prevention	Active	40 to 75	NCI	CHNMC-IRB-03178 NCT00100893

Special Category: NCI Avon award trial

Objectives

1. 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.
2. 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.
3. Determine, preliminarily, an optimum biologic dose of this dietary supplement, as defined by suppression of serum estradiol, in these participants.
4. Determine a minimum duration of use of this dietary supplement to achieve aromatase inhibition in these participants.

Entry Criteria

Disease Characteristics:

• At risk of developing breast cancer



• No history of breast cancer or ductal carcinoma in situ

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

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/mm³
• WBC ≥ 3,500/mm³
• Absolute granulocyte count ≥ 1,500/mm³
• 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)

Expected Enrollment

A total of 24 participants will be accrued for this study within 12 months.

Outcomes

Estrogen suppression as measured by serum estradiol, estrone, estrone sulfate, and sex hormone binding globulin at 1, 2, 4, 8, and 12 weeks

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

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.

Trial Contact Information

Trial Lead Organizations

City of Hope Comprehensive Cancer Center

Clinical Trials Office - New Patient Services		Ph: 800-826-4673 Email: becomingapatient@coh.org

U.S.A.
California
	Duarte
	City of Hope Comprehensive Cancer Center
		Clinical Trials Office - City of Hope Comprehensive Cancer Center	Ph:  800-826-4673
			Email: becomingapatient@coh.org

Registry Information
Official Title		A Phase I Prevention Trial of ACTIVINTM Grape Seed Extract as an Aromatase Inhibitor In Healthy Postmenopausal Women at Risk for Breast Cancer
Trial Start Date		2005-01-14
Trial Completion Date		2008-05-30 (estimated)
Registered in ClinicalTrials.gov		NCT00100893
Date Submitted to PDQ		2004-11-18
Information Last Verified		2007-04-06
NCI Grant/Contract Number		CA33572