Phase II Double Blind Randomized Trial Evaluating the Biologic Effect of Levonorgestrel on the Double Blind Randomized Trial Evaluating the Biologic Effect of Levonorgestrel on the Ovarian Epithelium in Women at High Risk for Ovarian Cancer
Phase II Double Blind Randomized Trial Evaluating the Biologic Effect of Levonorgestrel on the Double Blind Randomized Trial Evaluating the Biologic Effect of Levonorgestrel on the Ovarian Epithelium in Women at High Risk for Ovarian Cancer
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.
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.
Inclusion Criteria:
At increased genetic risk for ovarian cancer AND planning to undergo risk-reducing salpingo-oophorectomy (RRSO)
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
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
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)