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


Phase 2
25 Years
50 Years
Not Enrolling
Female
Endometrial Cancer

Thank you

Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Outcome Measure:

Change in potential SEBs relevant to endometrial carcinogenesis.

Outcome Time Frame:

From baseline to completion of hormone therapy

Safety Issue:

No

Principal Investigator

Karen Lu

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2013-00466

NCT ID:

NCT00033358

Start Date:

February 2002

Completion Date:

Related Keywords:

  • Endometrial Cancer
  • Endometrial Neoplasms
  • Sarcoma, Endometrial Stromal
  • Adenoma
  • Colorectal Neoplasms, Hereditary Nonpolyposis

Name

Location

M D Anderson Cancer CenterHouston, Texas  77030