Clinical trial NCT00043082: S0200 Carboplatin With or Without Doxil in Patients With Recurrent Ovarian Cancer
Official title: A Phase III Study of Liposomal Doxorubicin Plus Carboplatin Versus Carboplatin in Platinum-Sensitive Patients With Recurrent Epithelial Ovarian and Peritoneal Carcinoma After Failure of Initial Platinum-Based Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ovarian Cancer
Peritoneal Cavity Cancer
Keywords: peritoneal cavity cancer
recurrent ovarian epithelial cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 61
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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. Combining more than one drug may kill more tumor cells. It is not yet known if carboplatin is more effective with or without liposomal doxorubicin in treating recurrent ovarian epithelial or primary peritoneal cancer.

PURPOSE: Randomized phase III trial to determine the effectiveness of carboplatin with or without liposomal doxorubicin in treating patients who have recurrent ovarian epithelial or primary peritoneal cancer.

Detailed description: OBJECTIVES:

* Compare overall survival of patients with platinum-sensitive recurrent ovarian epithelial or primary peritoneal cancer treated with carboplatin with or without pegylated doxorubicin HCl liposome.
* Compare progression-free survival, confirmed complete response rates, and time to treatment failure in patients treated with these regimens.
* Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease measurability (elevated CA 125 only vs nonmeasurable disease only with or without elevated CA 125 vs measurable disease), number of disease sites (2 or fewer vs 3 or more), and serous tumor histology (yes vs no). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive carboplatin IV over 15 minutes and pegylated doxorubicin HCl liposome IV over 1 hour on day 1.
* Arm II: Patients receive carboplatin IV as in arm I. Treatment in both arms repeats every 4 weeks for a total of 15 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 4 weeks, every 6 months for 3 years, and then annually for 7 years.

PROJECTED ACCRUAL: A total of 900 patients will be accrued for this study within 4 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed ovarian epithelial carcinoma

  * Stage III or IV disease at time of initial staging laparotomy
* Primary peritoneal and mixed Mullerian tumors allowed
* No borderline ovarian tumors
* Disease progression or recurrence after a progression-free and platinum-free interval of 6-24 months after completion of first-line platinum-based chemotherapy (either single agent or combination therapy)
* Disease progression or recurrence based solely on CA 125 elevation allowed, provided that one of the following is true:

  * Prior baseline CA 125 greater than 35 U/mL and subsequent normalization of no greater than 35 U/mL must have CA 125 greater than 2 times upper limit of normal (ULN) on 2 occasions at least 1 week apart
  * Prior baseline CA 125 greater than 35 U/mL that never normalized must have CA 125 greater than 2 times the nadir value on 2 occasions at least 1 week apart
  * Prior normal baseline CA 125 (no greater than 35 U/mL) must show CA 125 greater than 2 times ULN on 2 occasions at least 1 week apart
* No known brain metastases

PATIENT CHARACTERISTICS:

Age

* Not specified

Performance status

* Zubrod 0-1

Life expectancy

* Not specified

Hematopoietic

* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin at least 10 g/dL

Hepatic

* SGOT and/or SGPT no greater than 2 times upper limit of normal (ULN)
* Alkaline phosphatase no greater than 2 times ULN
* Bilirubin no greater than ULN

Renal

* Creatinine no greater than 1.9 mg/dL

Cardiovascular

* No New York Heart Association class II-IV cardiac disease
* No clinical evidence of congestive heart failure
* Ejection fraction greater than 50% by MUGA or 2-dimensional echocardiogram

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or incidental carcinoid cancer
* No evidence of active or uncontrolled infection
* No severe gastrointestinal symptoms (i.e., partial obstruction) and/or gastrointestinal bleeding or diarrhea
* No greater than grade 1 preexisting sensory neuropathy

PRIOR CONCURRENT THERAPY:

Biologic therapy

* At least 28 days since prior biologic consolidation therapy
* No concurrent immunotherapy

Chemotherapy

* See Disease Characteristics
* At least 28 days since prior non-platinum-containing consolidation chemotherapy
* No prior pegylated doxorubicin HCl liposome
* No prior cumulative anthracycline (e.g., doxorubicin, daunorubicin, epirubicin) dose in excess of 240 mg/m\^2
* No other concurrent chemotherapy

Endocrine therapy

* No concurrent hormonal therapy

Radiotherapy

* No prior abdominopelvic irradiation
* No concurrent radiotherapy

Surgery

* See Disease Characteristics
* At least 28 days since prior surgical debulking for disease progression or recurrence and recovered
* No concurrent surgery

Other

* No other prior treatment during the 6-24 month progression-free and platinum-free interval except up to 12 courses of consolidation therapy
* No other concurrent anticancer therapy

Primary outcomes:
measure: overall survival
timeFrame: ten years
Secondary outcomes:
measure: progression free survival and response
timeFrame: 10 years
measure: side effects
timeFrame: 15 months
Other outcomes:
Locations:
city: Mobile
country: United States
facility: MBCCOP - Gulf Coast
state: Alabama
city: Phoenix
country: United States
facility: CCOP - Western Regional, Arizona
state: Arizona
city: Phoenix
country: United States
facility: Veterans Affairs Medical Center - Phoenix (Carl T. Hayden)
state: Arizona
city: Tucson
country: United States
facility: Veterans Affairs Medical Center - Tucson
state: Arizona
city: Tucson
country: United States
facility: Arizona Cancer Center at University of Arizona Health Sciences Center
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Little Rock
country: United States
facility: Veterans Affairs Medical Center - Little Rock
state: Arkansas
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Fresno
country: United States
facility: California Cancer Center at Woodward Park Office
state: California
city: Loma Linda
country: United States
facility: Veterans Affairs Medical Center - Loma Linda (Pettis)
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Martinez
country: United States
facility: Veterans Affairs Outpatient Clinic - Martinez
state: California
city: Oakland
country: United States
facility: CCOP - Bay Area Tumor Institute
state: California
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: Santa Rosa
country: United States
facility: CCOP - Santa Rosa Memorial Hospital
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center at University of Colorado Health Sciences Center
state: Colorado
city: Denver
country: United States
facility: Veterans Affairs Medical Center - Denver
state: Colorado
city: Washington
country: United States
facility: MBCCOP - Howard University Cancer Center
state: District of Columbia
city: Tampa
country: United States
facility: Veterans Affairs Medical Center - Tampa (Haley)
state: Florida
city: Atlanta
country: United States
facility: CCOP - Atlanta Regional
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: Veterans Affairs Medical Center - Chicago (Westside Hospital)
state: Illinois
city: Decatur
country: United States
facility: CCOP - Central Illinois
state: Illinois
city: Hines
country: United States
facility: Veterans Affairs Medical Center - Hines
state: Illinois
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center at Loyola University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Veterans Affairs Medical Center - Wichita
state: Kansas
city: Lexington
country: United States
facility: Veterans Affairs Medical Center - Lexington
state: Kentucky
city: Lexington
country: United States
facility: Markey Cancer Center at University of Kentucky Chandler Medical Center
state: Kentucky
city: New Orleans
country: United States
facility: MBCCOP - LSU Health Sciences Center
state: Louisiana
city: New Orleans
country: United States
facility: Tulane Cancer Center at Tulane University Hospital and Clinic
state: Louisiana
city: New Orleans
country: United States
facility: Veterans Affairs Medical Center - New Orleans
state: Louisiana
city: Shreveport
country: United States
facility: Veterans Affairs Medical Center - Shreveport
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center - Shreveport
state: Louisiana
city: Boston
country: United States
facility: Cancer Research Center at Boston Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Veterans Affairs Medical Center - Detroit
state: Michigan
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Health System
state: Michigan
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: Royal Oak
country: United States
facility: CCOP - Beaumont
state: Michigan
city: Southfield
country: United States
facility: Providence Cancer Institute at Providence Hospital - Southfield
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Jackson
country: United States
facility: Veterans Affairs Medical Center - Jackson
state: Mississippi
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis University Hospital Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: CCOP - St. Louis-Cape Girardeau
state: Missouri
city: Springfield
country: United States
facility: CCOP - Cancer Research for the Ozarks
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Albuquerque
country: United States
facility: Veterans Affairs Medical Center - Albuquerque
state: New Mexico
city: Albuquerque
country: United States
facility: MBCCOP - University of New Mexico HSC
state: New Mexico
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Goldsboro
country: United States
facility: CCOP - Southeast Cancer Control Consortium
state: North Carolina
city: Cincinnati
country: United States
facility: Veterans Affairs Medical Center - Cincinnati
state: Ohio
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Dayton
country: United States
facility: Veterans Affairs Medical Center - Dayton
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Medical Center
state: Oklahoma
city: Portland
country: United States
facility: Cancer Institute at Oregon Health and Science University
state: Oregon
city: Portland
country: United States
facility: Veterans Affairs Medical Center - Portland
state: Oregon
city: Portland
country: United States
facility: CCOP - Columbia River Oncology Program
state: Oregon
city: Charleston
country: United States
facility: Veterans Affairs Medical Center - Charleston
state: South Carolina
city: Charleston
country: United States
facility: Hollings Cancer Center at 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: University of Tennessee Cancer Institute at Methodist Central Hospital
state: Tennessee
city: Memphis
country: United States
facility: Veterans Affairs Medical Center - Memphis
state: Tennessee
city: Amarillo
country: United States
facility: Harrington Cancer Center
state: Texas
city: Amarillo
country: United States
facility: Veterans Affairs Medical Center - Amarillo
state: Texas
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: San Antonio
country: United States
facility: Veterans Affairs Medical Center - San Antonio (Murphy)
state: Texas
city: Temple
country: United States
facility: Veterans Affairs Medical Center - Temple
state: Texas
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Salt Lake City
country: United States
facility: Veterans Affairs Medical Center - Salt Lake City
state: Utah
city: Seattle
country: United States
facility: CCOP - Virginia Mason Research Center
state: Washington
city: Seattle
country: United States
facility: Veterans Affairs Medical Center - Seattle
state: Washington
city: Seattle
country: United States
facility: Puget Sound Oncology Consortium
state: Washington
city: Tacoma
country: United States
facility: CCOP - Northwest
state: Washington
Study officials:
affiliation: University of Arizona
name: David S. Alberts, MD
role: STUDY_CHAIR
References:
citation: Alberts DS, Liu PY, Wilczynski SP, Clouser MC, Lopez AM, Michelin DP, Lanzotti VJ, Markman M; Southwest Oncology Group. Randomized trial of pegylated liposomal doxorubicin (PLD) plus carboplatin versus carboplatin in platinum-sensitive (PS) patients with recurrent epithelial ovarian or peritoneal carcinoma after failure of initial platinum-based chemotherapy (Southwest Oncology Group Protocol S0200). Gynecol Oncol. 2008 Jan;108(1):90-4. doi: 10.1016/j.ygyno.2007.08.075. Epub 2007 Oct 18.