Clinical trial NCT00016341: Combination Chemotherapy Compared With Hormone Therapy in Treating Patients With Recurrent, Stage III, or Stage IV Endometrial Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Endometrial Cancer
Keywords: stage III endometrial carcinoma
stage IV endometrial carcinoma
recurrent endometrial carcinoma
Lead sponsor: GOG Foundation
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-09-09
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

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