A Pharmacokinetic Study of Genistein, a Tyrosine Kinase Inhibitor

Cancer Clinical Trial

Official title:

A Pharmacokinetic Study of Genistein, a Tyrosine Kinase Inhibitor

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001696
• Other study ID #: 980099
• Secondary ID: 98-C-0099
• Status: Completed
• Phase: Phase 1
• First received: November 3, 1999
• Last updated: March 3, 2008
• Start date: April 1998
• Est. completion date: March 2001

Study information

• Verified date: April 2000
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

Genistein is a natural product found in soy beans; its consumption has been associated with a low incidence of metastatic prostate cancer. Genistein is a known protein-tyrosine kinase inhibitor, and in preclinical studies it has been shown to increase cell adhesion. Increases in cell adhesion in vivo would phenotypically reverse the first step in the metastatic cascade, potentially preventing metastasis formation, and is consistent with epidemiologic findings. This study seeks to determine the pharmacokinetics of genistein in humans by administering a single dose of genistein and performing a pharmacokinetic analysis. Patients will be treated with two formulations of genistein (a 43% genistein preparation or a 90% preparation). This is a phase I study, and patients will be treated on one of three dosing levels. Patients will be randomly assigned to receive one formulation first, followed by a washout period, and will then receive the second preparation (i.e. a randomized cross over design). Information from this study will be used to optimally design a multiple dose study wherein patients will be treated for longer periods of time.

Description:

Genistein is a natural product found in soy beans; its consumption has been associated with a low incidence of metastatic prostate cancer. Genistein is a known protein-tyrosine kinase inhibitor, and in preclinical studies it has been shown to increase cell adhesion. Increases in cell adhesion in vivo would phenotypically reverse the first step in the metastatic cascade, potentially preventing metastasis formation, and is consistent with epidemiologic findings. This study seeks to determine the pharmacokinetics of genistein in humans by administering a single dose of genistein and performing a pharmacokinetic analysis. Patients will be treated with two formulations of genistein (a 43% genistein preparation or a 90% preparation). This is a phase I study, and patients will be treated on one of three dosing levels. Patients will be randomly assigned to receive one formulation first, followed by a washout period, and will then receive the second preparation (i.e., a randomized cross over design). Information from this study will be used to optimally design a multiple dose study wherein patients will be treated for longer periods of time. The duration of this study is estimated to be about 4 weeks long for each patient.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: March 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Must be 18 years old or greater.

ECOG performance status of 0-1.

Individuals without a history of cancer are eligible, as are those with a history of cancer. Individuals with a history of cancer (excluding non-melanomatous skin cancer ) will need to submit their pathology slides for review in the Laboratory of Pathology, NCI.

Must be able to understand and give informed consent.

Life expectancy greater than 6 months.

Hgb greater than or equal to 8.0gm/dl, platelets greater than or equal to 100,000/microliters, ANC greater than or equal to 1000/microliters, creatinine less than or equal to 2.0/mg/dl, SGPT and SGOT less than or equal to 147 and 168 U/L, total bilirubin less than or equal to 2 mg/dl (patients with a higher level of bilirubin due to a familial defect in bilirubin metabolism will be considered on an individual basis).

No history of breast cancer.

No pregnant or breast feeding subjects.

Must not be HIV positive.

No history of venous thrombosis within the past year.

No medical conditions, which, in the opinion of the investigators would jeopardize either the patient or the integrity of the data obtained.

No patients who are currently receiving active therapy for neoplastic disorders. However, patients with prostate cancer who are on an LHRH agonist (e.g., Lupron or Zoladex), or who have undergone surgical castration, are eligible for study.

No patients who are on estrogen therapy.

No patients taking hormonal forms of contraception.

No patients with a known soy intolerance.

Study Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• Genistein

Locations

Country	Name	City	State
United States	National Cancer Institute (NCI)	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Adlercreutz H, Markkanen H, Watanabe S. Plasma concentrations of phyto-oestrogens in Japanese men. Lancet. 1993 Nov 13;342(8881):1209-10. — View Citation

Adlercreutz H. Western diet and Western diseases: some hormonal and biochemical mechanisms and associations. Scand J Clin Lab Invest Suppl. 1990;201:3-23. Review. — View Citation

Severson RK, Nomura AM, Grove JS, Stemmermann GN. A prospective study of demographics, diet, and prostate cancer among men of Japanese ancestry in Hawaii. Cancer Res. 1989 Apr 1;49(7):1857-60. — View Citation