Levonorgestrel in Preventing Ovarian Cancer in Patients at High Risk for Ovarian Cancer

Phase 2

Completed

Conditions: Ovarian Carcinoma

Interventions: Other: Laboratory Biomarker Analysis
Drug: Levonorgestrel
Other: Placebo

Registration Number: NCT00445887

Lead Sponsor: Gynecologic Oncology Group

Brief Summary: This randomized phase II trial is studying how well levonorgestrel works in preventing ovarian cancer in patients at high risk for ovarian cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of levonorgestrel may prevent ovarian cancer.

Detailed Description: PRIMARY OBJECTIVES:

I. Determine the impact of levonorgestrel on the relative frequency of apoptosis in the ovarian epithelium of patients at high risk for ovarian cancer.

SECONDARY OBJECTIVES:

I. Estimate the impact of this drug on proliferation and transforming growth factor-beta (TGF-beta) expression in the ovarian epithelium of these patients.

II. Assess the safety of this drug in these patients.

OUTLINE: This is a prospective, randomized, placebo-controlled, double-blind study. Patients are stratified according to menopausal status (premenopausal vs postmenopausal). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oral levonorgestrel once daily.

ARM II: Patients receive oral placebo once daily.

In both arms, treatment continues for 4-6 weeks in the absence of disease progression or unacceptable toxicity, including on the day of surgery. Patients then undergo prophylactic salpingo-oophorectomy. After completion of study therapy, patients are followed at 1 year.

NOTE: \* Patients who are unable to have surgery completed during the expected 4-6 weeks, may continue levonorgestrel or placebo for a time period no \> 5 months. Patients unable to undergo surgery within 5 months are removed from the study.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 60

Inclusion Criteria

At increased genetic risk for ovarian cancer AND planning to undergo risk-reducing salpingo-oophorectomy (RRSO)
- Has ≥ 1 intact ovary
Patients enrolled on clinical trial GOG-0199 and planning to undergo RRSO allowed
Submission of fixed ovarian tissue (FN01) required
Must meet 1 of the following additional criteria:
- Family of the patient has a documented deleterious BRCA1 or BRCA2 mutation and either the patient herself has tested positive for a deleterious BRCA1 or BRCA2 mutation or the patient has a first- or second-degree relative with a deleterious BRCA1 or BRCA2 mutation
  - No patient with a deleterious BRCA1 or BRCA2 mutation whose first- or second-degree relative has tested negative for the exact same mutation
- The family contains members with ≥ 2 ovarian* and/or breast cancers among the first- or second-degree relatives (male relatives must be counted) of the patient within the same lineage (this condition may be satisfied by multiple primary cancers in the same person or, where breast cancer is required to meet this criterion, ≥ 1 breast cancer must have been diagnosed prior to menopause or at age ≤ 50 years if age at menopause is unknown)
- The patient is of Ashkenazi Jewish ethnicity (lineage via the mother) with one first- degree or two second-degree maternal relatives with breast and/or ovarian cancer* (where breast cancer is required to meet this criterion, ≥ 1 breast cancer must have been diagnosed prior to menopause or at age ≤ 50 years if age at menopause is unknown)
- The probability of carrying a BRCA1 or BRCA2 mutation, given the family pedigree of breast and ovarian cancers, exceeds 20%, as calculated by BRCAPRO
No prior history of ovarian cancer, including low malignant potential cancers, or primary papillary serous carcinoma of the peritoneum
No prior or concurrent history of breast cancer, including ductal carcinoma in situ (DCIS) of the breast
- Women with a history of hormone receptor-negative breast cancer (both estrogen receptor-negative and progesterone receptor-negative) are eligible
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective nonhormonal contraception prior to the prophylactic salpingo-oophorectomy
No prior history of deep vein thrombosis, stroke, liver disease, or heart attack
No prior history of myocardial infarction
No known bleeding disorders or hypercoagulable states
No other malignancy, including ductal carcinoma in situ, within 1 year of systemic therapy, except for nonmelanoma skin cancer
No prior chemotherapy regimen lasting ≥ 12 months
No oral or intrauterine hormonal contraception or hormonal replacement therapy within the past 3 months or injectable medroxyprogesterone within the past 12 months
No intraperitoneal surgery within the past 3 months (including laparoscopy)
No prior or concurrent radiotherapy to the pelvis
No concurrent hormonal contraception
No concurrent tamoxifen, raloxifene, estrogen, progesterone-like hormones, or other hormonal medication (including hormone replacement therapy)

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (levonorgestrel)	Levonorgestrel	Patients receive oral levonorgestrel once daily.
Arm II (placebo)	Laboratory Biomarker Analysis	Patients receive oral placebo once daily.
Arm I (levonorgestrel)	Laboratory Biomarker Analysis	Patients receive oral levonorgestrel once daily.
Arm II (placebo)	Levonorgestrel	Patients receive oral placebo once daily.
Arm II (placebo)	Placebo	Patients receive oral placebo once daily.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events According to Grade as Determined by NCI CTCAE v.3.0	Up to 20 weeks	Participants were graded using CTCAE v.30 criteria. Grade 1 is the least severe grade. Each adverse event lists criteria for grading, grade 1 being mild, up to grade 5. Grade 4 is generally life threatening. Grade 5 is death.
Median Proportion Cells That Are Apoptotic in Epithelial Ovarian Tissue	Surgical specimen (4 - 6 weeks after entry)	The median proportion of cells that are considered to be apoptotic are counted in the ovarian tissue sample, among the total number of cells available in the sample slide.

Secondary Outcome Measures

Name	Time	Method
Proportion of Proliferation as Measured by Ki-67	Time of surgery (4 to 6 weeks after entry)
Patients With High Expression of Transforming Growth Factor-beta 1	Baseline to time of surgery (4 to 6 weeks)

Trial Locations

Locations (66): Elkhart Clinic
🇺🇸
Elkhart, Indiana, United States
Michiana Hematology Oncology PC-South Bend
🇺🇸
South Bend, Indiana, United States
University of Texas Medical Branch
🇺🇸
Galveston, Texas, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
🇺🇸
Columbus, Ohio, United States
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸
Indianapolis, Indiana, United States
Saint Vincent Hospital and Health Care Center
🇺🇸
Indianapolis, Indiana, United States
Women's Cancer Center of Nevada
🇺🇸
Las Vegas, Nevada, United States
University of California San Diego
🇺🇸
San Diego, California, United States
University of Minnesota/Masonic Cancer Center
🇺🇸
Minneapolis, Minnesota, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
🇺🇸
Orange, California, United States
Elkhart General Hospital
🇺🇸
Elkhart, Indiana, United States
Saint Elizabeth Medical Center South
🇺🇸
Edgewood, Kentucky, United States
NorthShore University HealthSystem-Evanston Hospital
🇺🇸
Evanston, Illinois, United States
CoxHealth South Hospital
🇺🇸
Springfield, Missouri, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
🇺🇸
New York, New York, United States
Michiana Hematology Oncology PC-Plymouth
🇺🇸
Plymouth, Indiana, United States
Memorial Health University Medical Center
🇺🇸
Savannah, Georgia, United States
Michiana Hematology Oncology PC-Elkhart
🇺🇸
Elkhart, Indiana, United States
Bronson Methodist Hospital
🇺🇸
Kalamazoo, Michigan, United States
Mercy Hospital Springfield
🇺🇸
Springfield, Missouri, United States
Brooke Army Medical Center
🇺🇸
Fort Sam Houston, Texas, United States
Borgess Medical Center
🇺🇸
Kalamazoo, Michigan, United States
Huntsman Cancer Institute/University of Utah
🇺🇸
Salt Lake City, Utah, United States
Carilion Clinic Gynecological Oncology
🇺🇸
Roanoke, Virginia, United States
Lakeland Medical Center Saint Joseph
🇺🇸
Saint Joseph, Michigan, United States
University of Wisconsin Hospital and Clinics
🇺🇸
Madison, Wisconsin, United States
Dartmouth Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
Case Western Reserve University
🇺🇸
Cleveland, Ohio, United States
Cone Health Cancer Center at Alamance Regional
🇺🇸
Burlington, North Carolina, United States
University of Cincinnati/Barrett Cancer Center
🇺🇸
Cincinnati, Ohio, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
Miami Valley Hospital
🇺🇸
Dayton, Ohio, United States
Hinsdale Hematology Oncology Associates Incorporated
🇺🇸
Hinsdale, Illinois, United States
Saint Joseph Regional Medical Center-Mishawaka
🇺🇸
Mishawaka, Indiana, United States
Michiana Hematology Oncology PC-Mishawaka
🇺🇸
Mishawaka, Indiana, United States
Memorial Hospital of South Bend
🇺🇸
South Bend, Indiana, United States
Northern Indiana Cancer Research Consortium
🇺🇸
South Bend, Indiana, United States
IU Health La Porte Hospital
🇺🇸
La Porte, Indiana, United States
Michiana Hematology Oncology PC-Westville
🇺🇸
Westville, Indiana, United States
Baptist Health Lexington
🇺🇸
Lexington, Kentucky, United States
City of Hope Comprehensive Cancer Center
🇺🇸
Duarte, California, United States
USC / Norris Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
Sudarshan K Sharma MD Limited-Gynecologic Oncology
🇺🇸
Hinsdale, Illinois, United States
West Michigan Cancer Center
🇺🇸
Kalamazoo, Michigan, United States
Marie Yeager Cancer Center
🇺🇸
Saint Joseph, Michigan, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States
Cleveland Clinic Cancer Center/Fairview Hospital
🇺🇸
Cleveland, Ohio, United States
UH Seidman Cancer Center at Lake Health Mentor Campus
🇺🇸
Mentor, Ohio, United States
Cancer Research for the Ozarks NCORP
🇺🇸
Springfield, Missouri, United States
Rutgers Cancer Institute of New Jersey
🇺🇸
New Brunswick, New Jersey, United States
Good Samaritan Hospital - Cincinnati
🇺🇸
Cincinnati, Ohio, United States
University of Virginia Cancer Center
🇺🇸
Charlottesville, Virginia, United States
Lakeland Hospital Niles
🇺🇸
Niles, Michigan, United States
FirstHealth of the Carolinas-Moore Regional Hospital
🇺🇸
Pinehurst, North Carolina, United States
Hillcrest Hospital Cancer Center
🇺🇸
Mayfield Heights, Ohio, United States
Marshfield Medical Center-Marshfield
🇺🇸
Marshfield, Wisconsin, United States
Riverside Methodist Hospital
🇺🇸
Columbus, Ohio, United States
The Don and Sybil Harrington Cancer Center
🇺🇸
Amarillo, Texas, United States
Lehigh Valley Hospital-Cedar Crest
🇺🇸
Allentown, Pennsylvania, United States
Colorado Gynecologic Oncology Group
🇺🇸
Aurora, Colorado, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States