Ovarian Cancer
Conditions
Keywords
Ovarian epithelial cancer, High risk, Biomarkers
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.
Interventions
DRUGflutamide
Patients receive oral flutamide (125 MG/DAY) once daily for 6 weeks in the absence of unacceptable toxicity.
Sponsors
National Cancer Institute (NCI)
University of Arizona
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 83 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Colony Stimulating Factor (CSF-1) Expression in Ovarian Endosalpingiosis | Surgery | 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 | Surgery | CSF-1 levels were measured by immunohistochemistry (IHC). |
| Colony Stimulating Factor (CSF-1) Expression in Ovarian Stroma | Surgery | CSF-1 levels were measured by immunohistochemistry (IHC). |
| Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Endosalpingiosis | Surgery | CSF-1R levels were measured by immunohistochemistry (IHC). |
| Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Epithelium | Surgery | CSF-1R levels were measured by immunohistochemistry (IHC). |
| Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Stroma | Surgery | CSF-1R levels were measured by immunohistochemistry (IHC). |
| Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Endosalpingiosis | Surgery | ErbB4 levels were measured by immunohistochemistry (IHC). |
| Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Epithelium | Surgery | ErbB4 levels were measured by immunohistochemistry (IHC). |
| Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Stroma | Surgery | ErbB4 levels were measured by immunohistochemistry (IHC). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the medical clinic prior to oophorectomy. Participants were recruited from January 2007 until June 2011.
Pre-assignment details
Participants were assigned to groups immediately after being enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm Patients received oral flutamide (125 MG) once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent risk-reducing salpingo-oophorectomy.
flutamide: Patients receive oral flutamide (125 MG/DAY) once daily for 6 weeks in the absence of unacceptable toxicity. | 12 |
| High Risk Arm High risk patients underwent risk-reducing salpingo-oophorectomy. | 47 |
| Low Risk Arm Low risk patients underwent salpingo-oophorectomy for a medical indication. | 48 |
| Total | 107 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | No usable sample | 0 | 9 | 8 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Treatment Arm | High Risk Arm | Low Risk Arm | Total |
|---|---|---|---|---|
| Age, Continuous | 45.2 years | 46.9 years | 51.7 years | 48.9 years |
| Region of Enrollment United States | 12 participants | 47 participants | 48 participants | 107 participants |
| Sex: Female, Male Female | 12 Participants | 47 Participants | 48 Participants | 107 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 12 | 0 / 47 | 0 / 48 |
| serious Total, serious adverse events | 0 / 12 | 0 / 47 | 0 / 48 |
Outcome results
Primary
Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Endosalpingiosis
CSF-1R levels were measured by immunohistochemistry (IHC).
Time frame: Surgery
Population: The Overall Number of Participants Analyzed represents all participants with a modified Histo-score that could be evaluated
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Arm | Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Endosalpingiosis | 15 Histo-score (H-Score) |
| High Risk Arm | Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Endosalpingiosis | 160 Histo-score (H-Score) |
| Low Risk Arm | Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Endosalpingiosis | 75 Histo-score (H-Score) |
p-value: 0.009Wilcoxon Rank Sum Test
p-value: >0.05Wilcoxon Rank Sum Test
Primary
Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Epithelium
CSF-1R levels were measured by immunohistochemistry (IHC).
Time frame: Surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Arm | Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Epithelium | 0 Histo-score (H-Score) |
| High Risk Arm | Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Epithelium | 40 Histo-score (H-Score) |
| Low Risk Arm | Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Epithelium | 20 Histo-score (H-Score) |
p-value: 0.037Wilcoxon Rank Sum Test
p-value: >0.05Wilcoxon Rank Sum Test
Primary
Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Stroma
CSF-1R levels were measured by immunohistochemistry (IHC).
Time frame: Surgery
Population: The Overall Number of Participants Analyzed represents all participants with a modified Histo-score that could be evaluated
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Arm | Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Stroma | 20 Histo-score (H-Score) |
| High Risk Arm | Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Stroma | 40 Histo-score (H-Score) |
| Low Risk Arm | Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Stroma | 53 Histo-score (H-Score) |
p-value: 0.01Wilcoxon Rank Sum Test
p-value: >0.05Wilcoxon Rank Sum Test
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.
Time frame: Surgery
Population: The Overall Number of Participants Analyzed represents all participants with a modified Histo-score that could be evaluated
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Arm | Colony Stimulating Factor (CSF-1) Expression in Ovarian Endosalpingiosis | 5 Modified H-Score |
| High Risk Arm | Colony Stimulating Factor (CSF-1) Expression in Ovarian Endosalpingiosis | 130 Modified H-Score |
| Low Risk Arm | Colony Stimulating Factor (CSF-1) Expression in Ovarian Endosalpingiosis | 50 Modified H-Score |
p-value: 0.012Wilcoxon Rank Sum Test
p-value: >0.05Wilcoxon Rank Sum Test
Primary
Colony Stimulating Factor (CSF-1) Expression in Ovarian Epithelium
CSF-1 levels were measured by immunohistochemistry (IHC).
Time frame: Surgery
Population: The Overall Number of Participants Analyzed represents all participants with a modified Histo-score that could be evaluated
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Arm | Colony Stimulating Factor (CSF-1) Expression in Ovarian Epithelium | 0 Histo-score (H-Score) |
| High Risk Arm | Colony Stimulating Factor (CSF-1) Expression in Ovarian Epithelium | 50 Histo-score (H-Score) |
| Low Risk Arm | Colony Stimulating Factor (CSF-1) Expression in Ovarian Epithelium | 0 Histo-score (H-Score) |
p-value: 0.01Wilcoxon Rank Sum Test
p-value: 0.005Wilcoxon Rank Sum Test
Primary
Colony Stimulating Factor (CSF-1) Expression in Ovarian Stroma
CSF-1 levels were measured by immunohistochemistry (IHC).
Time frame: Surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Arm | Colony Stimulating Factor (CSF-1) Expression in Ovarian Stroma | 5 Histo-score (H-Score) |
| High Risk Arm | Colony Stimulating Factor (CSF-1) Expression in Ovarian Stroma | 40 Histo-score (H-Score) |
| Low Risk Arm | Colony Stimulating Factor (CSF-1) Expression in Ovarian Stroma | 35 Histo-score (H-Score) |
p-value: 0.0006Wilcoxon Rank Sum Test
p-value: >0.05Wilcoxon Rank Sum Test
Primary
Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Endosalpingiosis
ErbB4 levels were measured by immunohistochemistry (IHC).
Time frame: Surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Arm | Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Endosalpingiosis | 5 Histo-score (H-Score) |
| High Risk Arm | Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Endosalpingiosis | 60 Histo-score (H-Score) |
| Low Risk Arm | Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Endosalpingiosis | 10 Histo-score (H-Score) |
p-value: 0.005Wilcoxon Rank Sum Test
p-value: >0.05Wilcoxon Rank Sum Test
Primary
Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Epithelium
ErbB4 levels were measured by immunohistochemistry (IHC).
Time frame: Surgery
Population: The Overall Number of Participants Analyzed represents all participants with a modified Histo-score that could be evaluated
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Arm | Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Epithelium | 0 Histo-score (H-Score) |
| High Risk Arm | Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Epithelium | 55 Histo-score (H-Score) |
| Low Risk Arm | Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Epithelium | 0 Histo-score (H-Score) |
p-value: 0.006Wilcoxon Rank Sum Test
p-value: 0.005Wilcoxon Rank Sum Test
Primary
Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Stroma
ErbB4 levels were measured by immunohistochemistry (IHC).
Time frame: Surgery
Population: The Overall Number of Participants Analyzed represents all participants with a modified Histo-score that could be evaluated
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Arm | Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Stroma | 10 Histo-score (H-Score) |
| High Risk Arm | Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Stroma | 90 Histo-score (H-Score) |
| Low Risk Arm | Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Stroma | 30 Histo-score (H-Score) |
p-value: <0.0001Wilcoxon Rank Sum Test
p-value: 0.005Wilcoxon Rank Sum Test