Clinical trial NCT00699907: Effect of Flutamide on Biomarkers in Blood and Tissue Samples From Patients at High Risk of Ovarian Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: Ovarian epithelial cancer
High risk
Biomarkers
Lead sponsor: University of Arizona
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-06-18
Enrollment: 127
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 83
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Colony Stimulating Factor (CSF-1) Expression in Ovarian Endosalpingiosis
timeFrame: Surgery
measure: Colony Stimulating Factor (CSF-1) Expression in Ovarian Epithelium
timeFrame: Surgery
measure: Colony Stimulating Factor (CSF-1) Expression in Ovarian Stroma
timeFrame: Surgery
measure: Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Endosalpingiosis
timeFrame: Surgery
measure: Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Epithelium
timeFrame: Surgery
measure: Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Stroma
timeFrame: Surgery
measure: Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Endosalpingiosis
timeFrame: Surgery
measure: Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Epithelium
timeFrame: Surgery
measure: Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Stroma
timeFrame: Surgery
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
Study officials:
affiliation: University of Arizona Arizona Cancer Center
name: Setsuko K. Chambers, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gruessner C, Gruessner A, Glaser K, AbuShahin N, Zhou Y, Laughren C, Wright H, Pinkerton S, Yi X, Stoffer J, Azodi M, Zheng W, Chambers SK. Flutamide and biomarkers in women at high risk for ovarian cancer: preclinical and clinical evidence. Cancer Prev Res (Phila). 2014 Sep;7(9):896-905. doi: 10.1158/1940-6207.CAPR-13-0408. Epub 2014 Jun 20.