Effect of Flutamide on Biomarkers in Blood and Tissue Samples From Patients at High Risk of Ovarian Cancer

Ovarian Cancer Clinical Trial

Official title:

A Prospective, Phase IIA Study of the Effect of Flutamide (125 MG/DAY) Taken for 6 Weeks on Expression of Potential Biomarkers of Flutamide Action in the Ovaries of Women at Increased Risk for Ovarian Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00699907
• Other study ID #: 04-0707-04
• Secondary ID: P30CA023074
• Status: Completed
• Phase: Phase 2
• Start date: January 2005
• Est. completion date: November 2014

Study information

• Verified date: December 2017
• Source: University of Arizona
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Studying samples of blood and tissue in the laboratory from patients with a high risk of developing ovarian cancer may help doctors identify and learn more about biomarkers related to cancer. We hypothesized that (i) preclinical biologic evidence exists for the role of androgens in ovarian cancer development and (ii) flutamide treatment of women at high risk for ovarian cancer may identify meaningful tissue biomarkers of androgen action and of ovarian cancer initiation. This phase II trial studied the effect of flutamide on biomarkers in blood and tissue samples from patients at high risk of ovarian cancer.

Description:

OBJECTIVE: Compare the biomarkers of patients at high risk for ovarian cancer who are undergoing prophylactic oophorectomy and are interested in taking flutamide vs patients at high risk for ovarian cancer who are undergoing prophylactic oophorectomy and are not interested in taking flutamide (control) vs patients who are undergoing oophorectomy for a medical indication (control).

OUTLINE: Patients who elected not to receive flutamide received prophylactic oophorectomy or oophorectomy for a medical indication. Patients who elected to receive flutamide received 125mg once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent prophylactic oophorectomy. All patients underwent blood and ovarian tissue sample collection at the time of surgery for biomarker laboratory studies. Proteomic, microarray, and polymorphism analysis were performed on the blood and tissue samples.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: November 2014
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 83 Years

Eligibility

Inclusion Criteria for all patients:

• = 18 years of age

• Able to comply with study and follow-up requirements

Inclusion Criteria for high risk patients:

• elected to undergo prophylactic salpingo-oophorectomy

• fertile patients must use effective non-hormonal contraception

• agreed to use a nonhormonal means of contraception before surgery

• serum bilirubin = 1.0 x Upper Limit Normal (ULN), alkaline phosphatase, Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) = 2.5 x ULN

• serum creatinine = 1.5 x ULN

• granulocyte count = 1500/µL

• platelet count = 75,000/µL

• hemoglobin = 9 g/dL

• adequate complete blood count

• At high risk for developing ovarian cancer, as defined by any of the following:

• Breast Cancer carried a BRCA1 or BRCA2 deleterious mutation, a Lynch syndrome mutation, and/or defined by a family history of: 1 first-degree relative with epithelial ovarian cancer, =1 first-degree female relative with breast cancer when =40 years old, =1 first-degree female relative with breast cancer when =50 years old, male relative with breast cancer, and/or family history of breast cancer or ovarian cancer.

Inclusion Criteria for low risk patients:

• planning to undergo oophorectomy for a medical indication

• did not fulfill criteria for high risk of developing ovarian cancer

Exclusion criteria:

• liver disease, current alcohol abuse, or cirrhosis

• pregnancy or lactation

• current use of hormone therapy

• active treatment for cancer

• recent, current, or planned participation in another experimental drug study

• breast cancer within the past 5 years

• significant traumatic injury within the past 6 months

• major surgery within the past 6 months

• any disease, physical examination findings, or clinical laboratory findings giving reasonable suspicion of a disease or condition that contraindicates the continued use of an investigational drug or that may render the patient at high risk from treatment complication

Related Conditions & MeSH terms

• Neoplasms, Glandular and Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• flutamide
Patients receive oral flutamide (125 MG/DAY) once daily for 6 weeks in the absence of unacceptable toxicity.

Locations

Country	Name	City	State
United States	University of Arizona Cancer Center	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
University of Arizona	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Colony Stimulating Factor (CSF-1) Expression in Ovarian Endosalpingiosis	CSF-1 levels were measured by immunohistochemistry (IHC).; The modified H-Score assess extent of nuclear immunoreactivity applicable to steroid receptors.; The modified H-scores total range is 0-300. A lower modified H-score indicates weakly staining nuclei. A higher modified H-score indicated strongly staining nuclei.; This applies to all measures.	Surgery
Primary	Colony Stimulating Factor (CSF-1) Expression in Ovarian Epithelium	CSF-1 levels were measured by immunohistochemistry (IHC).	Surgery
Primary	Colony Stimulating Factor (CSF-1) Expression in Ovarian Stroma	CSF-1 levels were measured by immunohistochemistry (IHC).	Surgery
Primary	Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Endosalpingiosis	CSF-1R levels were measured by immunohistochemistry (IHC).	Surgery
Primary	Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Epithelium	CSF-1R levels were measured by immunohistochemistry (IHC).	Surgery
Primary	Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Stroma	CSF-1R levels were measured by immunohistochemistry (IHC).	Surgery
Primary	Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Endosalpingiosis	ErbB4 levels were measured by immunohistochemistry (IHC).	Surgery
Primary	Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Epithelium	ErbB4 levels were measured by immunohistochemistry (IHC).	Surgery
Primary	Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Stroma	ErbB4 levels were measured by immunohistochemistry (IHC).	Surgery

External Links

•   American Journal of Cancer Research, 2014.
•   Cancer Prevention Research, 2014.