Mesothelioma Related Clinical Trials:
Pemetrexed Plus Gemcitabine Or Carboplatin In Patients With Advanced Malignant Mesothelioma: A Randomized Phase II Trial

• Response rate by RECIST Criteria at every 2 courses [ Designated as safety issue: No ]
  

• Toxicity by Common Toxicity Criteria at each course [ Designated as safety issue: Yes ]
  
• Survival time [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Compare the response rates in patients with advanced malignant mesothelioma of the pleura treated with pemetrexed disodium combined with either gemcitabine or carboplatin.

Secondary

• Compare the relative toxic effects of these regimens in these patients.
• Compare 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.

• Arm I: Patients receive pemetrexed disodium IV 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.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced mesothelioma of the pleura
• Measurable disease
  • Unmeasurable pleural rinds allowed provided disease is evaluable by mesothelioma response criteria
  • The following are not considered measurable disease:
    • Pleural effusions
    • Positive bone scans
• Not a candidate for curative surgery
• No known or suspected brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• 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

Renal

• Creatinine clearance ≥ 45 mL/min OR
• Creatinine ≤ 2.0 g/dL

Other

• Able to take folic acid and cyanocobalamin (vitamin B12)
• Willing and able to take dexamethasone
• Not obviously malnourished
• No weight loss > 10% within the past 6 weeks
• No active infection
• No other serious systemic disorder that would preclude study participation
• No other malignancy within the past 3 years except carcinoma in situ of the cervix or breast, other in situ malignancies, or adequately treated basal cell skin cancer
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior intracavitary immunomodulators except for the purpose of pleurodesis

Chemotherapy

• No prior systemic chemotherapy for mesothelioma

Endocrine therapy

• Not specified

Radiotherapy

• Prior radiotherapy to the target lesion allowed provided both of the following criteria are met:

  • The lesion is clearly progressing after prior radiotherapy according to RECIST criteria
  • At least 4 weeks since prior radiotherapy

Surgery

• See Biologic therapy
• More than 2 weeks since prior pleurodesis

Other

• More than 4 weeks since prior investigational agents
• No prior intracavitary cytotoxic drugs except for the purpose of pleurodesis
• No 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)