RATIONALE: Hormone therapy may prevent the development of endometrial carcinogenesis (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.

PURPOSE: 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.

Condition	Treatment or Intervention	Phase
Endometrial Cancer hereditary non-polyposis colon cancer (hMSH2, hMLH1, hPMS1, hPMS2)	Drug: ethinyl estradiol  Drug: medroxyprogesterone  Drug: norgestrel  Procedure: cancer prevention intervention  Procedure: chemoprevention of cancer	Phase II

Further Study Details: 

OBJECTIVES:

• Compare the effect of medroxyprogesterone vs ethinyl estradiol and norgestrel on potential surrogate endpoint biomarkers relevant to endometrial carcinogenesis in women with a known hereditary non-polyposis colon cancer (HNPCC)-associated gene mutation or HNPCC-associated cancer(s).
• Compare the 3-month changes in histology and ultrasound appearance of the endometrium in patients treated with these preventive regimens.

OUTLINE: This is a randomized, multicenter study. 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 and oral placebo once daily on days 22-28. 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.

PROJECTED ACCRUAL: A total of 68 patients (34 per arm) will be accrued for this study within 22.7-34 months.

Ages Eligible for Study:  25 Years   -   50 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Meets criteria for 1 of the following:
• Known hereditary non-polyposis colon cancer (HNPCC)-associated mutation of MLH1, MSH2, MSH3, MSH6, PMS1, or PMS2 identified by gene sequencing
• Fulfills Amsterdam criteria with 1 or more HNPCC-associated cancers
• No known or suspected malignancy of the breast or endometrium
• Must have had a screening mammogram within the past 12 months if age 40 or over

PATIENT CHARACTERISTICS: Age:

• 25 to 50

Sex:

• Female

Menopausal status:

• No postmenopausal patients with amenorrhea for more than 1 year

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• No liver dysfunction or disease (e.g., hepatic adenomas or carcinoma)
• Liver function tests normal

Renal:

• Not specified

Cardiovascular:

• No active thrombophlebitis
• No prior or concurrent thromboembolic disorders or cerebrovascular disease
• No concurrent hypertension that is not well controlled
• No coronary artery disease

Other:

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during the first month of study therapy
• No undiagnosed vaginal bleeding
• No gallbladder disease
• No hypersensitivity to medroxyprogesterone contraceptive injection
• No concurrent uncontrolled depression
• No prior or concurrent epilepsy
• No prior or concurrent diabetes
• No tobacco smoking for patients age 35 to 50
• No alcohol dependence or illicit drug use
• No other significant medical history or psychiatric problems that would preclude study participation
• Fasting triglycerides no greater than 400 mg/dL
• Cholesterol no greater than 240 mg/dL
• Low-density lipoprotein (LDL) no greater than 160 mg/dL
• High-density lipoprotein (HDL) at least 35 mg/dL

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• At least 2 years since prior chemotherapy

Endocrine therapy:

• At least 4 months since prior oral contraceptives, medroxyprogesterone, or other hormonal exposure (e.g., hormonal intrauterine device, tamoxifen, raloxifene, or other selective estrogen receptor modulators)
• At least 4 months since prior systemic steroids (e.g., prednisone)
• No concurrent systemic steroids (e.g., prednisone)

Radiotherapy:

• No prior pelvic irradiation

Surgery:

• At least 3 months since prior endometrial biopsy, hysteroscopy, dilation and curettage, or placement of an intrauterine device
• No prior hysterectomy (patients may be scheduled for a prophylactic hysterectomy)
• No prior bilateral oophorectomy

Other:

• No other concurrent participation in a protocol with pharmacological intervention

Texas
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4009,  United States; Recruiting

Study chairs or principal investigators

Karen H. Lu, MD,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000069277; MDA-ID-01340; NCI-P02-0218; NCT00033358
Record last reviewed:  February 2004
Last Updated:  February 7, 2005
Record first received:  April 9, 2002
ClinicalTrials.gov Identifier:  NCT00033358
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08