Clinical trial NCT00003691: Combination Chemotherapy With or Without G-CSF in Treating Patients With Stage III, Stage IV, or Recurrent Endometrial Cancer
Official title: A Randomized Study of Doxorubicin Plus Cisplatin Versus Doxorubicin Plus Cisplatin Plus 3-Hour Paclitaxel With G-CSF Support in Patients With Primary Stage III & IV or Recurrent Endometrial Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
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: 2004-06-24
Enrollment: 240
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy consisting of doxorubicin and cisplatin with or without paclitaxel and G-CSF in treating patients who have stage III, stage IV, or recurrent endometrial cancer.

Detailed description: OBJECTIVES:

* Determine whether the addition of paclitaxel, using filgrastim (G-CSF) support, to standard doxorubicin/cisplatin chemotherapy produces improvement in the frequency of objective response, progression-free survival, or overall survival in patients with stage III, stage IV, or recurrent endometrial carcinoma.
* Compare the toxicities of these two regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive doxorubicin IV over 15-30 minutes, followed immediately by cisplatin IV over 1 hour.
* Arm II: Patients receive doxorubicin and cisplatin as in arm I on day 1. On day 2, patients receive paclitaxel IV over 3 hours. Patients also receive filgrastim (G-CSF) subcutaneously beginning on day 3 and continuing for at least 10 days.

Courses are repeated every 21 days. Treatment continues for up to 7 courses in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A total of 240 patients (120 per arm) will be accrued for this study within 21 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed primary stage III, stage IV, or recurrent endometrial carcinoma

  * Very poor potential for cure by radiotherapy or surgery alone or in combination
* Measurable disease

  * Disease in an irradiated field as the only site of measurable disease allowed provided there has been clear progression since completion of radiotherapy

PATIENT CHARACTERISTICS:

Age

* 18 and over

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

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

Renal

* Creatinine no greater than 1.6 mg/dL

Cardiovascular

* LVEF at least 50% within past 6 months
* No uncontrolled angina
* No third-degree or complete heart block unless a pacemaker is in place

Neurologic

* No serious peripheral neuropathy

Other

* No prior or concurrent malignancy within past 5 years except nonmelanoma skin cancer
* No uncontrolled infection
* No sensitivity to E. coli-derived drug preparations

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Prior biologic therapy allowed
* No concurrent biologic therapy

Chemotherapy

* No prior cytotoxic chemotherapy, including chemotherapy used for radiation sensitization
* No prior chemotherapy for any prior malignancy

Endocrine therapy

* Prior hormone therapy allowed
* No concurrent hormone therapy

Radiotherapy

* At least 4 weeks since prior radiotherapy to the whole pelvis or to over 50% of the spine

Surgery

* Not specified

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Comprehensive Cancer Center
state: Alabama
city: Phoenix
country: United States
facility: CCOP - Greater Phoenix
state: Arizona
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center
state: California
city: Palo Alto
country: United States
facility: Women's Cancer Center
state: California
city: Denver
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Washington
country: United States
facility: Vincent T. Lombardi Cancer Research Center, Georgetown University
state: District of Columbia
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: Atlanta
country: United States
facility: Emory University Hospital - Atlanta
state: Georgia
city: Honolulu
country: United States
facility: MBCCOP - Hawaii
state: Hawaii
city: Chicago
country: United States
facility: MBCCOP - University of Illinois at Chicago
state: Illinois
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: Decatur
country: United States
facility: CCOP - Central Illinois
state: Illinois
city: Evanston
country: United States
facility: CCOP - Evanston
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Lexington
country: United States
facility: Albert B. Chandler Medical Center, University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Oncology Center
state: Maryland
city: Bethesda
country: United States
facility: Medicine Branch
state: Maryland
city: Bethesda
country: United States
facility: Radiation Oncology Branch
state: Maryland
city: Boston
country: United States
facility: Tufts University School of Medicine
state: Massachusetts
city: Worcester
country: United States
facility: Memorial Hospital
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: CCOP - Ann Arbor Regional
state: Michigan
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: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Keesler AFB
country: United States
facility: Keesler Medical Center - Keesler AFB
state: Mississippi
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
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: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester 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 of Wake Forest University Baptist Medical Center
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 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: Tulsa
country: United States
facility: CCOP - Sooner State
state: Oklahoma
city: Portland
country: United States
facility: CCOP - Columbia River Program
state: Oregon
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: Pennsylvania Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: CCOP - MainLine Health
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Memphis
country: United States
facility: CCOP - Baptist Cancer Institute
state: Tennessee
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: University of Texas - MD Anderson Cancer Center
state: Texas
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Charlottesville
country: United States
facility: Cancer Center, University of Virginia HSC
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Tacoma
country: United States
facility: Tacoma General Hospital
state: Washington
city: Kingston
country: Canada
facility: NCIC-Clinical Trials Group
state: Ontario
Study officials:
affiliation: University of Chicago
name: Gini F. Fleming, MD
role: STUDY_CHAIR
References:
citation: Farley JH, Tian C, Rose GS, Brown CL, Birrer M, Risinger JI, Thigpen JT, Fleming GF, Gallion HH, Maxwell GL. Chemotherapy intensity and toxicity among black and white women with advanced and recurrent endometrial cancer: a Gynecologic Oncology Group Study. Cancer. 2010 Jan 15;116(2):355-61. doi: 10.1002/cncr.24769.
citation: Moore KN, Tian C, McMeekin DS, Thigpen JT, Randall ME, Gallion HH. Does the progression-free interval after primary chemotherapy predict survival after salvage chemotherapy in advanced and recurrent endometrial cancer?: a Gynecologic Oncology Group ancillary data analysis. Cancer. 2010 Dec 1;116(23):5407-14. doi: 10.1002/cncr.25480. Epub 2010 Aug 24.
citation: McMeekin DS, Filiaci VL, Thigpen JT, Gallion HH, Fleming GF, Rodgers WH; Gynecologic Oncology Group study. The relationship between histology and outcome in advanced and recurrent endometrial cancer patients participating in first-line chemotherapy trials: a Gynecologic Oncology Group study. Gynecol Oncol. 2007 Jul;106(1):16-22. doi: 10.1016/j.ygyno.2007.04.032.
citation: Modesitt SC, Tian C, Kryscio R, Thigpen JT, Randall ME, Gallion HH, Fleming GF; Gynecologic Oncology Group. Impact of body mass index on treatment outcomes in endometrial cancer patients receiving doxorubicin and cisplatin: a Gynecologic Oncology Group study. Gynecol Oncol. 2007 Apr;105(1):59-65. doi: 10.1016/j.ygyno.2006.10.045. Epub 2006 Dec 5.
citation: Maxwell GL, Tian C, Risinger J, Brown CL, Rose GS, Thigpen JT, Fleming GF, Gallion HH, Brewster WR; Gynecologic Oncology Group study. Racial disparity in survival among patients with advanced/recurrent endometrial adenocarcinoma: a Gynecologic Oncology Group study. Cancer. 2006 Nov 1;107(9):2197-205. doi: 10.1002/cncr.22232.
citation: Modesitt S, Tian C, Kryscio R, et al.: Impact of body mass index (BMI) on treatment outcomes in advanced or recurrent endometrial cancer patients receiving doxorubicin/cisplatin chemotherapy: a Gynecologic Oncology Group study. [Abstract] Society of Gynecologic Oncologists, 2006 Annual Meeting on Women's Cancer, March 22-26, 2006, Palm Springs, CA. A-93, 2006.
citation: Fleming GF, Brunetto VL, Cella D, Look KY, Reid GC, Munkarah AR, Kline R, Burger RA, Goodman A, Burks RT. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2004 Jun 1;22(11):2159-66. doi: 10.1200/JCO.2004.07.184.
citation: Fleming GF, Brunetto VL, Mundt AJ, et al.: Randomized trial of doxorubicin (DOX) plus cisplatin (CIS) versus DOX plus CIS plus paclitaxel (TAX) in patients with advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group (GOG) study. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-807, 2002.
citation: Huang HQ, Brady MF, Cella D, Fleming G. Validation and reduction of FACT/GOG-Ntx subscale for platinum/paclitaxel-induced neurologic symptoms: a gynecologic oncology group study. Int J Gynecol Cancer. 2007 Mar-Apr;17(2):387-93. doi: 10.1111/j.1525-1438.2007.00794.x.
citation: Grushko TA, Filiaci VL, Mundt AJ, Ridderstrale K, Olopade OI, Fleming GF; Gynecologic Oncology Group. An exploratory analysis of HER-2 amplification and overexpression in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2008 Jan;108(1):3-9. doi: 10.1016/j.ygyno.2007.09.007. Epub 2007 Oct 18.