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A Randomized, Controlled Phase II Evaluation of Megestrol (Megace®) in Different Dose and Sequence in the Treatment of Endometrial Intraepithelial Neoplasia (EIN) From a Referred Cohort of Atypical Endometrial Hyperplasia (AEH) or EIN


Phase 2
18 Years
N/A
Open (Enrolling)
Female
Endometrial Cancer, Precancerous Condition

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Trial Information

A Randomized, Controlled Phase II Evaluation of Megestrol (Megace®) in Different Dose and Sequence in the Treatment of Endometrial Intraepithelial Neoplasia (EIN) From a Referred Cohort of Atypical Endometrial Hyperplasia (AEH) or EIN


OBJECTIVES:

Primary

- To determine the frequency of complete of remission of a community biopsy diagnosis of
atypical endometrial hyperplasia (AEH) or endometrial intraepithelial neoplasia (EIN)
at the time of hysterectomy in patients treated with continuous versus interrupted
progestin therapy.

- To determine the frequency of complete remission of central pathology panel diagnosed
EIN patients treated with continuous versus interrupted progestin therapy. (Patients
who did not receive progestin treatment closed to accrual as of 8/3/2010)

Secondary

- To compare the quality-of-life (mood, concerns about weight, and bleeding) of patients
treated with these regimens.

- To assess the expression levels of PTEN in tumor tissue and its association with
response in patients treated with these regimens.

- To assess the expression levels of hormone receptors, estrogen and progesterone, in
tumor tissue, and their association with response in patients treated with these
regimens.

- To assess histomorphometry and karyometry characteristics of pre-treatment biopsy in
these patients.

- To identify patterns of protein and glycoprotein expression associated with invasive
cancer in serum specimens obtained from patients with a diagnosis of AEH or EIN.

- To assess differences in plasma concentrations of megestrol acetate among these
patients using high-performance liquid chromatography (HPLC).

- To assess patient compliance to their treatment regimen using HPLC to determine plasma
concentrations of megestrol.

- To explore the correlation between megestrol concentrations using HPLC and
pharmacodynamic response as assessed in hysterectomy specimens.

OUTLINE: Patients are stratified according to the collection method of the initial/intake
biopsy (dilatation and curettage vs all other methods). Patients are randomized to 1 of the
following treatment regimens:

- Regimen 1: Patients receive oral megestrol twice daily every day for 24 weeks.
Approximately twelve weeks after treatment starts, clinical blood tests are obtained
and research serum and plasma collected. Twenty-four weeks constitutes one course of
treatment and a pill count is performed during the 12-week f/u visit and at the
completion of the treatment course to determine compliance. After progestin therapy the
patient has an induced-withdrawal bleed. Patients in this arm undergo a re-evaluation
biopsy and hysterectomy a minimum of two weeks and a maximum of eight weeks after
completing the megestrol treatment.

- Regimen 2: Patients receive oral megestrol twice daily for two weeks continuously
followed by no treatment for two weeks. This course is repeated for a total of 24
weeks. Approximately twelve weeks after treatment starts, clinical blood tests are
obtained and research serum and plasma collected. Twenty-four weeks constitutes one
course of treatment and a pill count is performed during the 12-week f/u visit and at
the completion of the treatment course to determine compliance. After progestin therapy
the patient has an induced-withdrawal bleed. Patients in this arm undergo a
re-evaluation biopsy and hysterectomy a minimum of two weeks and a maximum of eight
weeks after the megestrol treatment.

- Regimen 3 (Closed as of 6/3/2010): Patients do not receive megestrol. At the discretion
of the managing physician, patients undergo the re-evaluation biopsy and hysterectomy
anytime between 2-20 weeks after enrollment and randomization.

Patients undergo biopsy and blood sample collection periodically for immunological and
pharmacodynamic studies. Samples are analyzed for presence or absence of myoinvasion or deep
myoinvasion in hysterectomy specimens, hormone receptivity status, and to compare PTEN
status against treatment via karyometry or morphometry, expression of VEGF and tenascin-C
(TN-C) via ELISA, presence of TN-C fragmentation via western immunoblots, additional
biomarkers via proteomic analysis, protein and glycoprotein expression patterns via
electrophoresis and image analysis, and plasma megestrol concentrations via high-performance
liquid chromatography (HPLC).

Patients complete the Hospital Anxiety and Depression Scale (HADS) and two items on bleeding
and weight gain at baseline and periodically during study. A Treatment Decision Assessment
is completed at baseline, and for patients withdrawing from the study, a Study Withdraw
Assessment is also completed.

There will be no additional follow-up on this study after the patient's hysterectomy.


DISEASE CHARACTERISTICS:

-

Inclusion Criteria:



- Histologically confirmed atypical endometrial hyperplasia (AEH) or endometrial
intraepithelial neoplasia (EIN)

- Diagnosed by dilatation and curettage (D&C), Novak curettage, Vabra
aspirate, or Pipelle endometrial biopsy at the enrolling institution within
6 weeks of enrollment

- Must agree to a hysterectomy

- Exclusion Criteria:

- Patients with recognized endometrial carcinoma

PATIENT CHARACTERISTICS:

-

Inclusion Criteria:



- GOG performance status 0-2

- WBC ≥ 3,000/mm^3

- Platelets ≥ 100,000/mm^3

- Granulocytes ≥ 1,500/mm^3

- Creatinine ≤ 2 mg/dL

- Bilirubin ≤ 1.5 x institutional upper limit normal

- SGOT and alkaline phosphatase ≤ 3 x institutional upper limit normal

- Patients of childbearing potential must have a negative serum pregnancy test
within 14 days of enrollment and must use appropriate nonhormonal contraception
while on study

- Exclusion Criteria:

- GOG performance status of 3 or 4

- Patients who cannot complete the study

- Patients who are considered inoperable

- Patients with current or prior history of breast cancer

- Patients with invasive malignancies, with the exception of nonmelanoma skin
cancer who had (or have) any evidence of the other cancer present within the
past 5 years or whose previous cancer treatment contraindicates this protocol
therapy

- Patients who are pregnant or lactating

- Patients with a history of thrombophlebitis, thromboembolic phenomena, or
cerebrovascular disorders

PRIOR CONCURRENT THERAPY:

- Exclusion Criteria:

- Patients who have received prior radiotherapy to any portion of the abdominal
cavity or pelvis are excluded

- Patients who have received prior chemotherapy for any abdominal or pelvic tumor
are excluded

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Number of patients who have responded to their respective treatment as determined by their re-evaluation biopsy and hysterectomy specimens

Safety Issue:

No

Principal Investigator

Michael W. Method, MD, MPH

Investigator Role:

Study Chair

Investigator Affiliation:

Michiana Hematology-Oncology, PC - South Bend

Authority:

United States: Federal Government

Study ID:

CDR0000555427

NCT ID:

NCT00503581

Start Date:

July 2007

Completion Date:

Related Keywords:

  • Endometrial Cancer
  • Precancerous Condition
  • high-grade squamous intraepithelial lesion
  • stage 0 endometrial carcinoma
  • Neoplasms
  • Endometrial Neoplasms
  • Endometrial Hyperplasia
  • Hyperplasia
  • Precancerous Conditions
  • Adenoma

Name

Location

George Bray Cancer Center at the Hospital of Central Connecticut - New Britain CampusNew Britain, Connecticut  06050
Memorial Hospital of South BendSouth Bend, Indiana  46601
CCOP - Cancer Research for the OzarksSpringfield, Missouri  65807
CCOP - Northern Indiana CR ConsortiumSouth Bend, Indiana  46601
Saint Joseph Regional Medical CenterSouth Bend, Indiana  46617
St. John's Regional Health CenterSpringfield, Missouri  65804
SUNY Downstate Medical CenterBrooklyn, New York  11203
Albert Einstein Cancer Center at Albert Einstein College of MedicineBronx, New York  10461
Oklahoma University Cancer InstituteOklahoma City, Oklahoma  73104
Virginia Commonwealth University Massey Cancer CenterRichmond, Virginia  23298-0037
Robert H. Lurie Comprehensive Cancer Center at Northwestern UniversityChicago, Illinois  60611
Elkhart General HospitalElkhart, Indiana  46515
Howard Community HospitalKokomo, Indiana  46904
Lakeland Regional Cancer Care Center - St. JosephSt. Joseph, Michigan  49085
Cancer Care Associates - Saint Francis CampusTulsa, Oklahoma  74136-1929
Center for Cancer Therapy at LaPorte Hospital and Health ServicesLa Porte, Indiana  46350
Michiana Hematology-Oncology, PC - ElkhartElkhart, Indiana  46514
Elkhart Clinic, LLCElkhart, Indiana  46514-2098
Michiana Hematology Oncology PC - La PorteLa Porte, Indiana  46350
Michiana Hematology-Oncology, PC - South BendMishawaka, Indiana  46545-1470
Michiana Hematology Oncology PC - PlymouthPlymouth, Indiana  46563
Lakeside Cancer Specialists, PLLCSaint Joseph, Michigan  49085
FirstHealth Moore Regional Community Hospital Comprehensive Cancer CenterPinehurst, North Carolina  28374
Duke Cancer InstituteDurham, North Carolina  27710
Women's Cancer Center - La CanadaLas Vegas, Nevada  89169
Olive View - UCLA Medical Center FoundationSylmar, California  91342