Pemetrexed Plus Gemcitabine or Carboplatin for Patients With Advanced Malignant Pleural Mesothelioma
Condition: Mesothelioma
MeSH terms: Mesothelioma; Mesothelioma, Malignant
Intervention: pemetrexed disodium; gemcitabine hydrochloride; carboplatin
Intervention description: 500 mg/m2 IV over 10 minutes on day 1 of a 21-day cycle; 1000 mg/m2 IV over 30 minutes on days 1 and 8 of a 21-day cycle; Given by IV over 30 minutes at an area under the curve (AUC) of 5 on day 1 of a 21-day cycle
Intervention MeSH terms: Carboplatin; Gemcitabine; Pemetrexed
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: advanced malignant mesothelioma; recurrent malignant mesothelioma

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.
    

Eligibility criteria:

        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)