Combination Chemotherapy Compared With Hormone Therapy in Treating Patients With Recurrent, Stage III, or Stage IV Endometrial Cancer

Randomized Phase III Crossover Trial of Chemotherapy (Doxorubicin/Cisplatin/Paclitaxel and G-CSF) Versus Hormonal Therapy (Tamoxifen/Megestrol Acetate) in Patients With Stage III & IV or Recurrent Endometrial Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Estrogen can stimulate the growth of tumor cells. Hormone therapy using tamoxifen and megestrol may fight endometrial cancer by blocking the absorption of estrogen. It is not yet known whether chemotherapy is more effective than hormone therapy in treating endometrial cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with that of hormone therapy in treating patients who have recurrent, stage III, or stage IV endometrial cancer.

Study Overview

• Status: Terminated
• Conditions: Endometrial Cancer
• Intervention / Treatment: Drug: cisplatin; Drug: doxorubicin hydrochloride; Drug: paclitaxel; Biological: filgrastim; Drug: tamoxifen citrate; Drug: megestrol acetate

Detailed Description

OBJECTIVES:

• Compare the progression-free survival and response of patients with stage III or IV or recurrent endometrial cancer treated with doxorubicin, cisplatin, paclitaxel, and filgrastim (G-CSF) vs tamoxifen and megestrol.
• Compare the survival of patients treated with these regimens.
• Determine if progesterone receptor status provides information on whether patients are more likely to benefit from chemotherapy.
• Compare the toxicity profiles of these treatment regimens in these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, cross-over, multicenter study. Patients are stratified according to progesterone receptor status (negative vs positive). Patients are randomized to 1 of 2 treatment arms.

• Arm I:Patients receive chemotherapy comprising doxorubicin IV over 15-30 minutes followed by cisplatin IV over 1 hour on day 1; paclitaxel IV over 3 hours on day 2; and filgrastim (G-CSF) subcutaneously beginning on day 3 and continuing for 10 days. Chemotherapy repeats every 21 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.
• At time of disease progression, patients cross-over to hormonal therapy as in arm II.
• Arm II: Patients receive hormonal therapy comprising oral megestrol twice daily on weeks 1-3 followed by oral tamoxifen twice daily on weeks 4-6. Hormonal therapy repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.

At time of disease progression, if patients have not previously been enrolled on arm I, patients cross-over to receive chemotherapy as in arm I.

Quality of life is assessed at baseline, 6 weeks, time of progression, and then after 6 weeks on cross-over therapy.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 630 patients will be accrued for this study within 42 months.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Center - Calgary
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama at Birmingham Comprehensive Cancer Center
  • California
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center, UCLA
    • Los Gatos, California, United States, 95032
      • Community Hospital of Los Gatos
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center
  • Colorado
    • Denver, Colorado, United States, 80010
      • University of Colorado Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20307-5000
      • Walter Reed Army Medical Center
  • Florida
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center and Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Cancer Research Center
    • Chicago, Illinois, United States, 60612
      • Rush-Presbyterian-St. Luke's Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5289
      • Indiana University Cancer Center
  • Iowa
    • Iowa City, Iowa, United States, 52242-1009
      • Holden Comprehensive Cancer Center at the University of Iowa
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0084
      • Albert B. Chandler Medical Center, University of Kentucky
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts University School of Medicine
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Cancer Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Medical Center
  • Missouri
    • Columbia, Missouri, United States, 65203
      • Ellis Fischel Cancer Center - Columbia
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital/University Medical Center
  • New York
    • Albany, New York, United States, 12208
      • Cancer Center of Albany Medical Center
    • Brooklyn, New York, United States, 11203
      • State University of New York Health Science Center at Brooklyn
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • Manhasset, New York, United States, 11030
      • Schneider Children's Hospital at North Shore
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
    • Stony Brook, New York, United States, 11790-7775
      • State University of New York Health Sciences Center - Stony Brook
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center, UNC
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Winston-Salem, North Carolina, United States, 27157-1082
      • Comprehensive Cancer Center at Wake Forest University
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0502
      • Barrett Cancer Center, The University Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Cleveland, Ohio, United States, 44106-5065
      • Ireland Cancer Center
    • Columbus, Ohio, United States, 43210-1240
      • Arthur G. James Cancer Hospital - Ohio State University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73190
      • University of Oklahoma College of Medicine
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Hershey, Pennsylvania, United States, 17033-0850
      • Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19104-4283
      • University of Pennsylvania Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107-5541
      • Kimmel Cancer Center of Thomas Jefferson University - Philadelphia
  • South Carolina
    • Charleston, South Carolina, United States, 29425-0721
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Brookview Research, Inc.
  • Texas
    • Dallas, Texas, United States, 75235-9154
      • Simmons Cancer Center - Dallas
    • Houston, Texas, United States, 77030-4009
      • University of Texas - MD Anderson Cancer Center
    • Houston, Texas, United States, 77030-4009
      • M.D. Anderson CCOP Research Base
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care - Medical Center Campus
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Cancer Center at the University of Virginia
  • Washington
    • Seattle, Washington, United States, 98109-1024
      • Fred Hutchinson Cancer Research Center
    • Tacoma, Washington, United States, 98405
      • Tacoma General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed primary stage III or IV or recurrent endometrial cancer
• Poor curative potential with radiotherapy or surgery (alone or in combination)

• Measurable disease

  • At least one lesion accurately measured in at least one dimension

    • At least 20 mm by conventional techniques, including palpation, x-ray, CT scan, or MRI OR
    • At least 10 mm by spiral CT scan
  • Disease in a previously irradiated field as sole site of measurable disease allowed only if clear progression after completion of radiotherapy

• Estrogen receptor(ER)/progesterone receptor (PR) status of primary tumor required

  • ER/PR status of measurable tumor optional

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• GOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Platelet count at least 100,000/mm^3
• Granulocyte count at least 1,500/mm^3

Hepatic:

• Bilirubin normal
• SGPT no greater than 3 times upper limit of normal

Renal:

• Creatinine no greater than 1.6 mg/dL

Cardiovascular:

• LVEF at least 50%
• No third-degree or complete heart block, unless pacemaker is in place
• Other conduction abnormalities or cardiac dysfunction allowed at the investigator's discretion
• No history of deep venous thrombosis
• No uncontrolled angina

Pulmonary:

• No history of pulmonary embolus

Other:

• No other malignancy within the past 5 years except nonmelanoma skin cancer
• No concurrent medical illness that would preclude study
• No serious uncontrolled infection
• No serious peripheral neuropathy
• No circumstances that would preclude study compliance
• No sensitivity to E. coli-derived drug preparations

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior biologic therapy allowed

Chemotherapy:

• No prior cytotoxic chemotherapy, including chemotherapy for radiosensitization

Endocrine therapy:

• No prior hormonal therapy for endometrial cancer

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy involving the whole pelvis or more than 50% of the spine

Surgery:

• See Disease Characteristics

Other:

• Concurrent cardiac conduction-altering medications such as digitalis, beta blockers, or calcium channel blockers allowed at the investigator's discretion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

Collaborators and Investigators

• Sponsor: Gynecologic Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Jeffrey D. Bloss, MD, Washington University Siteman Cancer Center

Study record dates

Study Major Dates

• Study Start: May 1, 2001
• Primary Completion (Actual): October 1, 2003

Study Registration Dates

• First Submitted: May 6, 2001
• First Submitted That Met QC Criteria: September 8, 2003
• First Posted (Estimate): September 9, 2003

Study Record Updates

• Last Update Posted (Estimate): April 11, 2013
• Last Update Submitted That Met QC Criteria: April 10, 2013
• Last Verified: June 1, 2007

More Information

Terms related to this study

• Keywords: stage IV endometrial carcinoma; recurrent endometrial carcinoma; stage III endometrial carcinoma
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endometrial Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Central Nervous System Stimulants; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Appetite Stimulants; Paclitaxel; Cisplatin; Doxorubicin; Liposomal doxorubicin; Tamoxifen; Megestrol; Megestrol Acetate
• Other Study ID Numbers: CDR0000068624; GOG-0189