Hormone Therapy in Preventing Endometrial Carcinogenesis (Cancer) in Women With a Genetic Risk For Hereditary Nonpolyposis Colon Cancer

Condition(s) targeted: Endometrial Cancer; Hereditary Non-Polyposis Colon Cancer (hmsh2, hmlh1, hpms1, hpms2)

Intervention: ethinyl estradiol (Drug); medroxyprogesterone (Drug); norgestrel (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Karen H. Lu, MD, Study Chair, Affiliation: M.D. Anderson Cancer Center

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.

Official title: Modulation Of Putative Surrogate Endpoint Biomarkers In Endometrial Biopsies From Women With HNPCC

Study design: Prevention, Randomized, Active Control

Primary outcome: Frequency of endometrial abnormalities by histology at baseline

Secondary outcome:

Changes in histology and ultrasound appearance at 3 months

Changes in surrogate endpoint biomarkers at 3 months

Detailed description: 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. 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 44 patients (22 per arm) will be accrued for this study.

Minimum age: 25 Years. Maximum age: 50 Years. Gender(s): Female.

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

UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California 94115, United States

Creighton University Medical Center, Omaha, Nebraska 68131-2197, United States

M. D. Anderson Cancer Center at University of Texas, Houston, Texas 77030-4009, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: February 2002
Last updated: June 12, 2008