Pemetrexed Plus Gemcitabine or Carboplatin for Patients With Advanced Malignant Pleural Mesothelioma
- Conditions
- Mesothelioma
- Interventions
- Registration Number
- NCT00101283
- Lead Sponsor
- Eastern Cooperative Oncology Group
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as pemetrexed disodium, gemcitabine, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether giving pemetrexed disodium with gemcitabine is more effective than giving pemetrexed disodium with carboplatin in treating malignant pleural mesothelioma.
PURPOSE: This randomized phase II trial is studying pemetrexed disodium with gemcitabine and pemetrexed disodium with carboplatin to see how well the combinations work compared to historical controls in treating patients with advanced malignant pleural mesothelioma.
- Detailed Description
OBJECTIVES:
Primary
* Estimate the response rates in patients with advanced malignant mesothelioma of the pleura treated with pemetrexed disodium combined with either gemcitabine or carboplatin.
Secondary
* Assess the toxic effects of these regimens in these patients.
* Estimate survival time in patients treated with these regimens.
* Correlate smoking status with outcome in patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms. While randomized, the study is not a comparative study. Rather, outcomes on each arm will be compared to a historical control rate from previous studies. Randomization allows simultaneous testing of two experimental arms.
* Arm I: Patients receive intravenous (IV) pemetrexed disodium over 10 minutes and carboplatin IV over 30 minutes on day 1.
* Arm II: Patients receive pemetrexed disodium as in arm I and gemcitabine IV over 30 minutes on days 1 and 8.
In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Beginning approximately 5-10 days before the start of chemotherapy and continuing until approximately 3 weeks after completion of chemotherapy, all patients receive oral folic acid once daily and cyanocobalamin (vitamin B12) intramuscularly every 9 weeks.
Patients are followed every 3 months for 2 years and then every 6 months for 1 year.
PROJECTED ACCRUAL: A total of 32-60 patients (16-30 per treatment arm) will be accrued for this study within 12.8-27.0 months.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
-
Histologically or cytologically confirmed advanced mesothelioma of the pleura
-
Measurable disease, as defined by RECIST criteria, within 4 weeks of randomization. Patients with pleural rinds not measurable by RECIST were eligible if disease was evaluable within 4 weeks of randomization using mesothelioma response criteria
-
May have undergone pleurodesis. If pleurodesis was performed, there must have been at least a 2-week delay before Pemetrexed administration. A CT must have been performed after 2 weeks after pleurodesis to serve as the baseline scan.
-
ECOG Performance Status of 0 or 1
-
Normal organ and marrow function, as defined by:
- Absolute neutrophil count ≥ 1,500/ul
- Platelet count ≥ 100,000/ul
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 3 times ULN (5 times ULN if liver has tumor involvement)
- Albumin ≥ 2.5 g/dL
- Creatinine clearance ≥ 45 mL/min or Creatinine ≤ 2.0 g/dL
-
Age 18 years and over
-
Able to take folic acid and cyanocobalamin (vitamin B12)
-
Willing and able to take dexamethasone
-
Women of childbearing potential and sexually active men were required to use contraception during and for the first 3 months after the study
Exclusion Criteria
- A candidate for curative surgery
- Prior radiation therapy to the target lesion, unless the lesion was clearly progressing per RECIST criteria after prior radiation and the interval between the most recent radiation therapy and enrollment was at least 4 weeks
- Prior systemic chemotherapy for mesothelioma. Prior intracavitary cytotoxic drugs or immunomodulators were not permitted, unless given for the purpose of pleurodesis.
- Active infection or serious concomitant systemic disorder
- Second primary malignancy, other than in situ malignancies or adequately treated basal cell carcinoma of the skin or other malignancy treated at least 3 years previously with no evidence of recurrence.
- Treatment with an investigational agent within 4 weeks before enrollment
- Known or suspected brain metastases
- Women must not be pregnant or breastfeeding
- Obviously malnourished or with a weight loss of greater than 10% in the preceding 6 weeks
- Aspirin or other nonsteroidal anti-inflammatory drugs for 2 days before, during, and for 2 days after each administration of pemetrexed disodium (5 days before, during, and 2 days after each administration of pemetrexed disodium for piroxicam, naproxen, diflunisal, or nabumetone)
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pemetrexed/Gemcitabine gemcitabine hydrochloride Pemetrexed disodium 500 mg/m2 IV over 10 minutes on day 1 and gemcitabine 1000 mg/m2 IV over 30 minutes on days 1 and 8 of a 21-day cycle. Pemetrexed/Gemcitabine pemetrexed disodium Pemetrexed disodium 500 mg/m2 IV over 10 minutes on day 1 and gemcitabine 1000 mg/m2 IV over 30 minutes on days 1 and 8 of a 21-day cycle. Pemetrexed/Carboplatin pemetrexed disodium Pemetrexed disodium 500 mg/m2 IV over 10 minutes and carboplatin to area under the curve (AUC) 5 IV over 30 minutes on day 1 of a 21-day cycle. Pemetrexed/Carboplatin carboplatin Pemetrexed disodium 500 mg/m2 IV over 10 minutes and carboplatin to area under the curve (AUC) 5 IV over 30 minutes on day 1 of a 21-day cycle.
- Primary Outcome Measures
Name Time Method Best Overall Response by RECIST Criteria (Version 1.0) Assessed every 2 cycles (6 weeks) while on treatment, then every 3 months for 2 years, then every 6 months for 1 year until disease progression Number of eligible, treated participants in each response category by RECIST criteria. Response categories represent best response for each patient prior to progression.
- Secondary Outcome Measures
Name Time Method Progression-Free Survival Assessed every 3 months for 2 years, then every 6 months for 1 year Time from randomization to the earlier of disease progression or death. Patients alive and progression-free at last follow-up were censored.
Overall Survival Assessed every 3 months for 2 years, then every 6 months for 1 year Time from randomization to death. Patients alive at last follow-up were censored.
Trial Locations
- Locations (115)
St. Rita's Medical Center
🇺🇸Lima, Ohio, United States
Fox Chase Cancer Center - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Mason District Hospital
🇺🇸Havana, Illinois, United States
Case Comprehensive Cancer Center
🇺🇸Cleveland, Ohio, United States
Indiana University Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Graham Hospital
🇺🇸Canton, Illinois, United States
CCOP - Illinois Oncology Research Association
🇺🇸Peoria, Illinois, United States
Oncology Hematology Associates of Central Illinois, PC - Peoria
🇺🇸Peoria, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
CCOP - Metro-Minnesota
🇺🇸Saint Louis Park, Minnesota, United States
Bismarck Cancer Center
🇺🇸Bismarck, North Dakota, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Meeker County Memorial Hospital
🇺🇸Litchfield, Minnesota, United States
Regions Hospital Cancer Care Center
🇺🇸Saint Paul, Minnesota, United States
HealthEast Cancer Care at St. Joseph's Hospital
🇺🇸Saint Paul, Minnesota, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Hennepin County Medical Center - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Miller - Dwan Medical Center
🇺🇸Duluth, Minnesota, United States
Mercy and Unity Cancer Center at Unity Hospital
🇺🇸Fridley, Minnesota, United States
St. Francis Cancer Center at St. Francis Medical Center
🇺🇸Shakopee, Minnesota, United States
Minnesota Oncology Hematology, PA - Maplewood
🇺🇸Maplewood, Minnesota, United States
CCOP - Duluth
🇺🇸Duluth, Minnesota, United States
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
🇺🇸Robbinsdale, Minnesota, United States
Park Nicollet Cancer Center
🇺🇸Saint Louis Park, Minnesota, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
HealthEast Cancer Care at St. John's Hospital
🇺🇸Maplewood, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Mercy and Unity Cancer Center at Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
HealthEast Cancer Care at Woodwinds Health Campus
🇺🇸Woodbury, Minnesota, United States
Minnesota Oncology Hematology, PA - Woodbury
🇺🇸Woodbury, Minnesota, United States
Mid Dakota Clinic, PC
🇺🇸Bismarck, North Dakota, United States
St. Alexius Medical Center Cancer Center
🇺🇸Bismarck, North Dakota, United States
Fox Chase Virtua Health Cancer Program at Virtua West Jersey
🇺🇸Voorhees, New Jersey, United States
CCOP - Christiana Care Health Services
🇺🇸Newark, Delaware, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Sparrow Regional Cancer Center
🇺🇸Lansing, Michigan, United States
Cancer Institute of New Jersey at Cooper - Voorhees
🇺🇸Voorhees, New Jersey, United States
Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
🇺🇸La Crosse, Wisconsin, United States
Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
🇺🇸Marlton, New Jersey, United States
Tunnell Cancer Center at Beebe Medical Center
🇺🇸Lewes, Delaware, United States
Union Hospital Cancer Program at Union Hospital
🇺🇸Elkton, Maryland, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Eastern Connecticut Hematology and Oncology Associates
🇺🇸Norwich, Connecticut, United States
Borgess Medical Center
🇺🇸Kalamazoo, Michigan, United States
Genesys Hurley Cancer Institute
🇺🇸Flint, Michigan, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
St. John Macomb Hospital
🇺🇸Warren, Michigan, United States
Sanford Cancer Center at Sanford USD Medical Center
🇺🇸Sioux Falls, South Dakota, United States
CCOP - Northern New Jersey
🇺🇸Hackensack, New Jersey, United States
Veterans Affairs Medical Center - East Orange
🇺🇸East Orange, New Jersey, United States
Hopedale Medical Complex
🇺🇸Hopedale, Illinois, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Saint Joseph Mercy Cancer Center
🇺🇸Ann Arbor, Michigan, United States
CCOP - Michigan Cancer Research Consortium
🇺🇸Ann Arbor, Michigan, United States
Medcenter One Hospital Cancer Care Center
🇺🇸Bismarck, North Dakota, United States
Rush-Copley Cancer Care Center
🇺🇸Aurora, Illinois, United States
St. Joseph Medical Center
🇺🇸Bloomington, Illinois, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
Memorial Hospital
🇺🇸Carthage, Illinois, United States
Galesburg Cottage Hospital
🇺🇸Galesburg, Illinois, United States
Decatur Memorial Hospital Cancer Care Institute
🇺🇸Decatur, Illinois, United States
Joliet Oncology-Hematology Associates, Limited - West
🇺🇸Joliet, Illinois, United States
Kewanee Hospital
🇺🇸Kewanee, Illinois, United States
BroMenn Regional Medical Center
🇺🇸Normal, Illinois, United States
Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
🇺🇸Moline, Illinois, United States
Community Cancer Center
🇺🇸Normal, Illinois, United States
Community Hospital of Ottawa
🇺🇸Ottawa, Illinois, United States
Cancer Treatment Center at Pekin Hospital
🇺🇸Pekin, Illinois, United States
Proctor Hospital
🇺🇸Peoria, Illinois, United States
Oncology Hematology Associates of Central Illinois, PC - Ottawa
🇺🇸Ottawa, Illinois, United States
OSF St. Francis Medical Center
🇺🇸Peoria, Illinois, United States
Illinois Valley Community Hospital
🇺🇸Peru, Illinois, United States
Perry Memorial Hospital
🇺🇸Princeton, Illinois, United States
St. Margaret's Hospital
🇺🇸Spring Valley, Illinois, United States
Elkhart General Hospital
🇺🇸Elkhart, Indiana, United States
Veterans Affairs Medical Center - Indianapolis
🇺🇸Indianapolis, Indiana, United States
Regional Cancer Center at Memorial Medical Center
🇺🇸Springfield, Illinois, United States
William N. Wishard Memorial Hospital
🇺🇸Indianapolis, Indiana, United States
Howard Community Hospital
🇺🇸Kokomo, Indiana, United States
Center for Cancer Therapy at LaPorte Hospital and Health Services
🇺🇸La Porte, Indiana, United States
Saint Anthony Memorial Health Centers
🇺🇸Michigan City, Indiana, United States
Memorial Hospital of South Bend
🇺🇸South Bend, Indiana, United States
CCOP - Northern Indiana CR Consortium
🇺🇸South Bend, Indiana, United States
McFarland Clinic, PC
🇺🇸Ames, Iowa, United States
Saint Joseph Regional Medical Center
🇺🇸South Bend, Indiana, United States
Cedar Rapids Oncology Associates
🇺🇸Cedar Rapids, Iowa, United States
Siouxland Hematology-Oncology Associates, LLP
🇺🇸Sioux City, Iowa, United States
St. Luke's Regional Medical Center
🇺🇸Sioux City, Iowa, United States
Oakwood Cancer Center at Oakwood Hospital and Medical Center
🇺🇸Dearborn, Michigan, United States
Foote Memorial Hospital
🇺🇸Jackson, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
Lakeland Regional Cancer Care Center - St. Joseph
🇺🇸Saint Joseph, Michigan, United States
Seton Cancer Institute at Saint Mary's - Saginaw
🇺🇸Saginaw, Michigan, United States
Hutchinson Area Health Care
🇺🇸Hutchinson, Minnesota, United States
Aultman Cancer Center at Aultman Hospital
🇺🇸Canton, Ohio, United States
Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
🇺🇸Allentown, Pennsylvania, United States
Penn State Cancer Institute at Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Lewistown Hospital
🇺🇸Lewistown, Pennsylvania, United States
Albert Einstein Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
Mount Nittany Medical Center
🇺🇸State College, Pennsylvania, United States
Eureka Community Hospital
🇺🇸Eureka, Illinois, United States
Galesburg Clinic, PC
🇺🇸Galesburg, Illinois, United States
McDonough District Hospital
🇺🇸Macomb, Illinois, United States
CCOP - Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Carle Cancer Center at Carle Foundation Hospital
🇺🇸Urbana, Illinois, United States
Mercy Medical Center - Sioux City
🇺🇸Sioux City, Iowa, United States
Duluth Clinic Cancer Center - Duluth
🇺🇸Duluth, Minnesota, United States
Summa Center for Cancer Care at Akron City Hospital
🇺🇸Akron, Ohio, United States
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
🇺🇸Madison, Wisconsin, United States
Medical X-Ray Center, PC
🇺🇸Sioux Falls, South Dakota, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center
🇺🇸Grosse Pointe Woods, Michigan, United States