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

Ovarian Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00445887
• Other study ID #: GOG-0214
• Secondary ID: NCI-2009-0058810
• Status: Completed
• Phase: Phase 2
• Start date: March 10, 2008

Study information

• Verified date: November 2019
• Source: Gynecologic Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 60
• Est. primary completion date: December 11, 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 30 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Ovarian Carcinoma
• Ovarian Neoplasms

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Levonorgestrel
Given orally

Other:
• Placebo
Given orally

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Gynecologic Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Median Proportion Cells That Are Apoptotic in Fallopian Tube Tissue	The median proportion of cells that are considered to be apoptotic are counted in the fallopian tube tissue sample, among the total number of cells available in the sample slide	Surgical specimen (4-6 weeks after entry)
Primary	Median Proportion Cells That Are Apoptotic in Epithelial Ovarian Tissue	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.	Surgical specimen (4 - 6 weeks after entry)
Primary	Number of Participants With Adverse Events According to Grade as Determined by NCI CTCAE v.3.0	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.	Up to 20 weeks
Secondary	Proportion of Proliferation as Measured by Ki-67		Time of surgery (4 to 6 weeks after entry)
Secondary	Patients With High Expression of Transforming Growth Factor-beta 1		Baseline to time of surgery (4 to 6 weeks)