Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Prevention	Completed	25 to 50	NCI	MDA-ID-01340 TX035, NCI-P02-0218, N01-CN-05127, NCT00033358

Objectives

1. 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).
2. Compare the 3-month changes in histology and ultrasound appearance of the endometrium in patients treated with these preventive regimens.

Entry 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

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

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

Expected Enrollment

A total of 44 patients (22 per arm) will be accrued for this study.

Outcomes

Frequency of endometrial abnormalities by histology at baseline

Changes in histology and ultrasound appearance at 3 months
Changes in surrogate endpoint biomarkers at 3 months

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.

Trial Contact Information

Trial Lead Organizations

M. D. Anderson Cancer Center at University of Texas

Karen Lu, MD, Protocol chair		Ph: 713-745-8902; 800-392-1611

Registry Information
Official Title		Modulation Of Putative Surrogate Endpoint Biomarkers In Endometrial Biopsies From Women With HNPCC
Trial Start Date		2002-02-12
Trial Completion Date		2009-09-15
Registered in ClinicalTrials.gov		NCT00033358
Date Submitted to PDQ		2002-02-07
Information Last Verified		2008-10-29
NCI Grant/Contract Number		CA16672, CN05127

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