Levonorgestrel in Preventing Ovarian Cancer in Patients 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.

Study Overview

• Status: Completed
• Conditions: Ovarian Carcinoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Placebo; Drug: Levonorgestrel

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Orange, California, United States, 92868
      • UC Irvine Health/Chao Family Comprehensive Cancer Center
    • San Diego, California, United States, 92103
      • University of California San Diego
  • Colorado
    • Aurora, Colorado, United States, 80010
      • Colorado Gynecologic Oncology Group
  • Georgia
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
    • Hinsdale, Illinois, United States, 60521
      • Hinsdale Hematology Oncology Associates Incorporated
    • Hinsdale, Illinois, United States, 60521
      • Sudarshan K Sharma MD Limited-Gynecologic Oncology
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Elkhart, Indiana, United States, 46514
      • Michiana Hematology Oncology PC-Elkhart
    • Elkhart, Indiana, United States, 46514-2098
      • Elkhart Clinic
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46260
      • Saint Vincent Hospital and Health Care Center
    • La Porte, Indiana, United States, 46350
      • IU Health La Porte Hospital
    • Mishawaka, Indiana, United States, 46545
      • Michiana Hematology Oncology PC-Mishawaka
    • Mishawaka, Indiana, United States, 46545
      • Saint Joseph Regional Medical Center-Mishawaka
    • Plymouth, Indiana, United States, 46563
      • Michiana Hematology Oncology PC-Plymouth
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46601
      • Michiana Hematology Oncology PC-South Bend
    • South Bend, Indiana, United States, 46628
      • Northern Indiana Cancer Research Consortium
    • Westville, Indiana, United States, 46391
      • Michiana Hematology Oncology PC-Westville
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Saint Elizabeth Medical Center South
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49048
      • Borgess Medical Center
    • Niles, Michigan, United States, 49120
      • Lakeland Hospital Niles
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Medical Center Saint Joseph
    • Saint Joseph, Michigan, United States, 49085
      • Marie Yeager Cancer Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota/Masonic Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Springfield, Missouri, United States, 65804
      • Cancer Research for the Ozarks NCORP
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Women's Cancer Center of Nevada
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10016
      • Laura and Isaac Perlmutter Cancer Center at NYU Langone
  • North Carolina
    • Burlington, North Carolina, United States, 27215
      • Cone Health Cancer Center at Alamance Regional
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center/Levine Cancer Institute
    • Pinehurst, North Carolina, United States, 28374
      • FirstHealth of the Carolinas-Moore Regional Hospital
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • Good Samaritan Hospital - Cincinnati
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati/Barrett Cancer Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital Cancer Center
    • Mentor, Ohio, United States, 44060
      • UH Seidman Cancer Center at Lake Health Mentor Campus
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital-Cedar Crest
  • Texas
    • Amarillo, Texas, United States, 79106
      • The Don and Sybil Harrington Cancer Center
    • Fort Sam Houston, Texas, United States, 78234
      • Brooke Army Medical Center
    • Galveston, Texas, United States, 77555-0565
      • University of Texas Medical Branch
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center
    • Roanoke, Virginia, United States, 24016
      • Carilion Clinic Gynecological Oncology
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Medical Center-Marshfield

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (levonorgestrel); Patients receive oral levonorgestrel once daily.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Levonorgestrel; Given orally; Other Names: Mirena; Plan B; 18-Methylnorethisterone; D-(-)-Norgestrel; L-norgestrel; Norplant
Placebo Comparator: Arm II (placebo); Patients receive oral placebo once daily.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Placebo; Given orally; Other Names: placebo therapy; PLCB; sham therapy; Drug: Levonorgestrel; Given orally; Other Names: Mirena; Plan B; 18-Methylnorethisterone; D-(-)-Norgestrel; L-norgestrel; Norplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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 Outcome Measures

Outcome Measure	Time Frame
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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Collaborators and Investigators

• Sponsor: Gynecologic Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Gustavo C Rodriguez, Gynecologic Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2008
• Primary Completion (Actual): December 11, 2013

Study Registration Dates

• First Submitted: March 7, 2007
• First Submitted That Met QC Criteria: March 7, 2007
• First Posted (Estimate): March 9, 2007

Study Record Updates

• Last Update Posted (Actual): November 19, 2019
• Last Update Submitted That Met QC Criteria: November 7, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Levonorgestrel; Norgestrel
• Other Study ID Numbers: GOG-0214 (Other Identifier: CTEP); U10CA101165 (U.S. NIH Grant/Contract); NCI-2009-00588 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 10-01367; CDR0000532268