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

NCT00699907 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 04-0707-04P30CA023074
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 1

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.

Conditions

Ovarian Cancer

Keywords

Ovarian epithelial cancer; High risk; Biomarkers

Outcome Measures

Primary Outcomes (9)

• 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

Study Arms (3)

Treatment Arm

ACTIVE COMPARATOR

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

High Risk Arm

NO INTERVENTION

High risk patients underwent risk-reducing salpingo-oophorectomy.

Low Risk Arm

NO INTERVENTION

Low risk patients underwent salpingo-oophorectomy for a medical indication.

Interventions

flutamide DRUG

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

Also known as: Eulexin, Cytomid, Cebatrol, Chimax, Drogenil, Flucinom, Flutamin, Fugerel, Niftolide, Sebatrol

Treatment Arm

Eligibility Criteria

• Age: 18 Years - 83 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years of age
• Able to comply with study and follow-up requirements
• 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.
• planning to undergo oophorectomy for a medical indication
• did not fulfill criteria for high risk of developing ovarian cancer

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Arizona: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Arizona Cancer Center

Tucson, Arizona, 85724-5024, United States

Location

Related Publications (1)

• 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.

  PMID: 24950779 DERIVED

Related Links

• American Journal of Cancer Research, 2014.

MeSH Terms

Conditions

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial

Interventions

Flutamide; Salicylic Acid

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Salicylates; Hydroxybenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols

Results Point of Contact

• Title: Dr. Setsuko K. Chambers
• Organization: University of Arizona

schamber@uacc.arizona.edu

520-626-0950

Study Officials

• Setsuko K. Chambers, MD

  University of Arizona Arizona Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2008
• First Posted: June 18, 2008
• Study Start: January 1, 2005
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2014
• Last Updated: July 24, 2018
• Results First Posted: January 5, 2018

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)