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

Gynecologic Oncology Group (GOG)

Status and phase: Completed; Phase 2

Conditions: Ovarian Carcinoma

Treatments: Other: Laboratory Biomarker Analysis; Drug: Levonorgestrel; Other: Placebo

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00445887

10-01367

NCI-2009-00588 (Registry Identifier)

GOG-0214

U10CA101165 (U.S. NIH Grant/Contract)

CDR0000532268

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 patients

Sex: Female

Ages: 30+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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60 participants in 2 patient groups, including a placebo group

Arm I (levonorgestrel)

Experimental group

Description:

Patients receive oral levonorgestrel once daily.

Treatment:

Drug: Levonorgestrel

Other: Laboratory Biomarker Analysis

Arm II (placebo)

Placebo Comparator group

Description:

Patients receive oral placebo once daily.

Treatment:

Other: Placebo

Drug: Levonorgestrel

Other: Laboratory Biomarker Analysis