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

Endometrial Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00016341
• Other study ID #: CDR0000068624
• Secondary ID: GOG-0189
• Status: Terminated
• Phase: Phase 3
• First received: May 6, 2001
• Last updated: April 10, 2013
• Start date: May 2001

Study information

• Verified date: June 2007
• Source: Gynecologic Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 0
• Est. primary completion date: October 2003
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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 Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms

Intervention

Biological:
• filgrastim

Drug:
• cisplatin

• doxorubicin hydrochloride

• megestrol acetate

• paclitaxel

• tamoxifen citrate

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Center - Calgary	Calgary	Alberta
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Cancer Center of Albany Medical Center	Albany	New York
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Tufts University School of Medicine	Boston	Massachusetts
United States	State University of New York Health Science Center at Brooklyn	Brooklyn	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Fletcher Allen Health Care - Medical Center Campus	Burlington	Vermont
United States	Cooper Hospital/University Medical Center	Camden	New Jersey
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Cancer Center at the University of Virginia	Charlottesville	Virginia
United States	Rush-Presbyterian-St. Luke's Medical Center	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Barrett Cancer Center, The University Hospital	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Ireland Cancer Center	Cleveland	Ohio
United States	Ellis Fischel Cancer Center - Columbia	Columbia	Missouri
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	University of Colorado Cancer Center	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	M.D. Anderson CCOP Research Base	Houston	Texas
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Holden Comprehensive Cancer Center at The University of Iowa	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Albert B. Chandler Medical Center, University of Kentucky	Lexington	Kentucky
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	Community Hospital of Los Gatos	Los Gatos	California
United States	Schneider Children's Hospital at North Shore	Manhasset	New York
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Brookview Research, Inc.	Nashville	Tennessee
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	University of Oklahoma College of Medicine	Oklahoma City	Oklahoma
United States	Chao Family Comprehensive Cancer Center	Orange	California
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center of Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	State University of New York Health Sciences Center - Stony Brook	Stony Brook	New York
United States	Tacoma General Hospital	Tacoma	Washington
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Gynecologic Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,