Pemetrexed Plus Gemcitabine or Carboplatin for Patients With Advanced Malignant Pleural Mesothelioma

Phase 2

Completed

Conditions: Mesothelioma

Interventions: Drug: pemetrexed disodium
Drug: gemcitabine hydrochloride
Drug: carboplatin

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

Inclusion Criteria

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)

Exclusion Criteria

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): Eastern Connecticut Hematology and Oncology Associates
🇺🇸
Norwich, Connecticut, United States
Tunnell Cancer Center at Beebe Medical Center
🇺🇸
Lewes, Delaware, United States
CCOP - Christiana Care Health Services
🇺🇸
Newark, Delaware, United States
Mayo Clinic - Jacksonville
🇺🇸
Jacksonville, Florida, United States
Winship Cancer Institute of Emory University
🇺🇸
Atlanta, Georgia, United States
Rush-Copley Cancer Care Center
🇺🇸
Aurora, Illinois, United States
St. Joseph Medical Center
🇺🇸
Bloomington, Illinois, United States
Graham Hospital
🇺🇸
Canton, Illinois, United States
Memorial Hospital
🇺🇸
Carthage, Illinois, United States
Decatur Memorial Hospital Cancer Care Institute
🇺🇸
Decatur, Illinois, United States
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Eastern Connecticut Hematology and Oncology Associates
🇺🇸Norwich, Connecticut, United States