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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: flutamide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 83 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment Arm<br>Patients received oral flutamide (125 MG) once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent risk-reducing salpingo-oophorectomy. | Drug: flutamide<br>* Patients receive oral flutamide (125 MG/DAY) once daily for 6 weeks in the absence of unacceptable toxicity.<br>* Other names: Sebatrol;|
| No Intervention: High Risk Arm<br>High risk patients underwent risk-reducing salpingo-oophorectomy. | |
| No Intervention: Low Risk Arm<br>Low risk patients underwent salpingo-oophorectomy for a medical indication. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Colony Stimulating Factor (CSF-1) Expression in Ovarian Epithelium | CSF-1 levels were measured by immunohistochemistry (IHC). | Surgery | 
| Colony Stimulating Factor (CSF-1) Expression in Ovarian Stroma | CSF-1 levels were measured by immunohistochemistry (IHC). | Surgery | 
| Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Endosalpingiosis | CSF-1R levels were measured by immunohistochemistry (IHC). | Surgery | 
| Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Epithelium | CSF-1R levels were measured by immunohistochemistry (IHC). | Surgery | 
| Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Stroma | CSF-1R levels were measured by immunohistochemistry (IHC). | Surgery | 
| Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Endosalpingiosis | ErbB4 levels were measured by immunohistochemistry (IHC). | Surgery | 
| Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Epithelium | ErbB4 levels were measured by immunohistochemistry (IHC). | Surgery | 
| Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Stroma | ErbB4 levels were measured by immunohistochemistry (IHC). | Surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian epithelial cancer, High risk, Biomarkers