Hormone Therapy in Preventing Endometrial Cancer in Patients With a Genetic Risk For Hereditary Nonpolyposis Colon Cancer

Tracking Information
First Submitted Date ICMJE	April 9, 2002
First Posted Date ICMJE	January 27, 2003
Last Update Posted Date	May 3, 2013
Study Start Date ICMJE	February 2002
Actual Primary Completion Date	October 2007 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: April 17, 2013)	Change in potential SEBs relevant to endometrial carcinogenesis. [ Time Frame: From baseline to completion of hormone therapy ]
Original Primary Outcome Measures ICMJE	Not Provided
Change History	Complete list of historical versions of study NCT00033358 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: April 17, 2013)	Changes in histology and ultrasound appearance of the endometrium in women with HNPCC [ Time Frame: From baseline to 3 months ]
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Hormone Therapy in Preventing Endometrial Cancer in Patients With a Genetic Risk For Hereditary Nonpolyposis Colon Cancer
Official Title ICMJE	Modulation Of Putative Surrogate Endpoint Biomarkers In Endometrial Biopsies From Women With HNPCC
Brief Summary	Randomized phase II trial to compare two different hormone therapy regimens in preventing endometrial cancer in women who have a genetic risk for hereditary nonpolyposis colon cancer. Hormone therapy may prevent the development of endometrial cancer in women with a genetic risk for hereditary nonpolyposis colon cancer. It is not yet known which hormone therapy regimen is more effective in preventing endometrial cancer.
Detailed Description	PRIMARY OBJECTIVES: I. The primary objective is to evaluate the effect of progesterone therapy versus combination estrogen and progesterone therapy on potential surrogate endpoint biomarkers (SEBs) relevant to endometrial carcinogenesis. II. To evaluate changes in histology and ultrasound appearance of the endometrium in women with HNPCC after 3 months of progesterone therapy versus combination estrogen and progesterone therapy compared with baseline. III. To establish a point estimate of the baseline frequency of endometrial abnormalities looking at histological and molecular markers in a cohort of females carrying an HNPCC gene mutation. OUTLINE: Patients are randomized to 1 of 2 arms. All patients undergo a baseline transvaginal ultrasound and endometrial biopsy. Arm I: Patients receive medroxyprogesterone intramuscularly once on day 1. Approximately 90 days after the injection, patients undergo a repeat transvaginal ultrasound and endometrial biopsy. Arm II: Patients receive oral contraceptive pills (OCP) comprising ethinyl estradiol and norgestrel once daily on days 1-21. Treatment repeats every 28 days for 3-4 courses (3-4 packs of OCP) in the absence of unacceptable toxicity. Approximately 1 week after starting the fourth pack of OCP, patients undergo a repeat transvaginal ultrasound and endometrial biopsy. Patients are followed at 6 weeks and are encouraged to return in 6 months to participate in continued endometrial screening.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
Condition ICMJE	Endometrial Cancer
Intervention ICMJE	Drug: medroxyprogesterone Given intramuscularly Other Names: Depo-Provera medroxyprogesterone acetate MPA Provera Provera Dosepak; Drug: ethinyl estradiol Given orally Other Names: Diogyn E EE Estinyl Ethinoral Eticylol; Drug: norgestrel Given orally Other Names: Microlut NORGES Ovrette Wy-3707; Other: laboratory biomarker analysis Correlative studies
Study Arms	Experimental: Arm I (medroxyprogesterone) Patients receive medroxyprogesterone intramuscularly once on day 1. Approximately 90 days after the injection, patients undergo a repeat transvaginal ultrasound and endometrial biopsy. Interventions: Drug: medroxyprogesterone Other: laboratory biomarker analysis; Experimental: Arm II (ethinyl estradiol, norgestrel) Patients receive OCP comprising ethinyl estradiol and norgestrel once daily on days 1-21. Treatment repeats every 28 days for 3-4 courses (3-4 packs of OCP) in the absence of unacceptable toxicity. Approximately 1 week after starting the fourth pack of OCP, patients undergo a repeat transvaginal ultrasound and endometrial biopsy. Interventions: Drug: ethinyl estradiol Drug: norgestrel Other: laboratory biomarker analysis
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: August 17, 2010)	52
Original Enrollment ICMJE	Not Provided
Study Completion Date	Not Provided
Actual Primary Completion Date	October 2007 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Women with known mutation of an HNPCC-associated gene (hMLH-1, hMSH-2, or hMSH-6) or fulfill Amsterdam Criteria and have had one or more HNPCC-associated cancers; No prior hysterectomy; (participants may be scheduled for prophylactic hysterectomy following the study); Voluntary consent documented by a signed and witnessed informed consent; Negative serum pregnancy test at baseline evaluation; No history of pelvic irradiation for whatever cause; No chemotherapy for two years; Women >= 40 must have had a screening mammogram within the last 12 months prior to participation in this study; Women who are at 50% risk of having a mutation and willing to have genetic testing Exclusion Criteria: Use of oral contraceptives or depoMPA or hormonal exposure, such as hormonal IUD, tamoxifen, raloxifene, or other selective estrogen receptor modulators (SERMs) within four months of initiating study; women will be asked to be off oral contraceptives or other hormonal exposure for 4 months prior to initiating study; Medical contraindication to use of oral contraceptives or depoMPA including: Known or suspected pregnancy Undiagnosed vaginal bleeding Known or suspected malignancy of breast or endometrium Active thrombophlebitis, or current or past history of thromboembolic disorders, or cerebral vascular disease Gall bladder disease or liver dysfunction or disease, including hepatic adenomas or carcinoma, or abnormal liver function tests Known hypersensitivity to depoMPA contraceptive injection (medroxyprogesterone acetate or any of its other ingredients) Depression that is currently not under control, in the judgement of the Principal Investigator History of epilepsy History of diabetes Coronary artery disease Age >=35 and a current tobacco smoker; Known inability to participate in the scheduled follow-up tests (i.e., alcohol dependence or illicit drug use); Significant medical history or psychiatric problems which would make the participant a poor protocol candidate, in the opinion of the principal investigator; Post surgical removal of both ovaries; Postmenopausal women with amenorrhea greater than 12 months; Previous history of endometrial biopsy, hysteroscopy, dilatation and curettage, or IUD in place within the past 3 months; Known participation in a concurrent protocol with a pharmacological intervention; Recent or concurrent use of systemic steroids (i.e. prednisone) within the past four months of initiating study; Positive serum pregnancy test at baseline evaluation; Fasting triglycerides level >= 400 mg/dl; Cholesterol level >= 240 mg/dl; LDL level >= 160 mg/dl; HDL level =< 35 mg/dl; Hypertension that is currently not under good control, in the judgement of the principal investigator
Sex/Gender	Sexes Eligible for Study: Female
Ages	25 Years to 50 Years (Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00033358
Other Study ID Numbers ICMJE	NCI-2013-00466; ID01-340; CDR0000069277; NCI-P02-0218; MDA-ID-01340; N01CN05127 ( Other Grant/Funding Number: US NIH Grant/Contract Award Number )
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	National Cancer Institute (NCI)
Study Sponsor ICMJE	National Cancer Institute (NCI)
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Karen Lu M.D. Anderson Cancer Center
PRS Account	National Cancer Institute (NCI)
Verification Date	April 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP