search
Back to results

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

Primary Purpose

Ovarian Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
flutamide
Sponsored by
University of Arizona
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Ovarian Cancer focused on measuring Ovarian epithelial cancer, High risk, Biomarkers

Eligibility Criteria

18 Years - 83 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • University of Arizona Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

No Intervention

No Intervention

Arm Label

Treatment Arm

High Risk Arm

Low Risk Arm

Arm Description

Patients received oral flutamide (125 MG) once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent risk-reducing salpingo-oophorectomy.

High risk patients underwent risk-reducing salpingo-oophorectomy.

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
June 17, 2008
Last Updated
June 27, 2018
Sponsor
University of Arizona
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00699907
Brief Title
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

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
January 2005 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Arizona
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
Keywords
Ovarian epithelial cancer, High risk, Biomarkers

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
127 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment Arm
Arm Type
Active Comparator
Arm Description
Patients received oral flutamide (125 MG) once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent risk-reducing salpingo-oophorectomy.
Arm Title
High Risk Arm
Arm Type
No Intervention
Arm Description
High risk patients underwent risk-reducing salpingo-oophorectomy.
Arm Title
Low Risk Arm
Arm Type
No Intervention
Arm Description
Low risk patients underwent salpingo-oophorectomy for a medical indication.
Intervention Type
Drug
Intervention Name(s)
flutamide
Other Intervention Name(s)
Eulexin, Cytomid, Cebatrol, Chimax, Drogenil, Flucinom, Flutamin, Fugerel, Niftolide, Sebatrol
Intervention Description
Patients receive oral flutamide (125 MG/DAY) once daily for 6 weeks in the absence of unacceptable toxicity.
Primary Outcome Measure Information:
Title
Colony Stimulating Factor (CSF-1) Expression in Ovarian Endosalpingiosis
Description
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.
Time Frame
Surgery
Title
Colony Stimulating Factor (CSF-1) Expression in Ovarian Epithelium
Description
CSF-1 levels were measured by immunohistochemistry (IHC).
Time Frame
Surgery
Title
Colony Stimulating Factor (CSF-1) Expression in Ovarian Stroma
Description
CSF-1 levels were measured by immunohistochemistry (IHC).
Time Frame
Surgery
Title
Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Endosalpingiosis
Description
CSF-1R levels were measured by immunohistochemistry (IHC).
Time Frame
Surgery
Title
Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Epithelium
Description
CSF-1R levels were measured by immunohistochemistry (IHC).
Time Frame
Surgery
Title
Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Stroma
Description
CSF-1R levels were measured by immunohistochemistry (IHC).
Time Frame
Surgery
Title
Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Endosalpingiosis
Description
ErbB4 levels were measured by immunohistochemistry (IHC).
Time Frame
Surgery
Title
Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Epithelium
Description
ErbB4 levels were measured by immunohistochemistry (IHC).
Time Frame
Surgery
Title
Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Stroma
Description
ErbB4 levels were measured by immunohistochemistry (IHC).
Time Frame
Surgery

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
83 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Setsuko K. Chambers, MD
Organizational Affiliation
University of Arizona Arizona Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724-5024
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
24950779
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.
Results Reference
derived
Links:
URL
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902233/
Description
American Journal of Cancer Research, 2014.

Learn more about this trial

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

We'll reach out to this number within 24 hrs