Pemetrexed Disodium and Gemcitabine in Treating Patients With Malignant Mesothelioma

http://www.clinicaltrials.gov/ct/show/NCT00060190?amp;order=6

RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy such as gemcitabine use different ways to stop tumor cells from dividing so they stop growing or die. Combining pemetrexed disodium with gemcitabine may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining pemetrexed disodium with gemcitabine in treating patients who have pleural or peritonealmalignant mesothelioma.

Official Title: Phase II Study of Pemetrexed Disodium and Gemcitabine in Chemotherapy-Naïve Patients With Malignant Pleural or Peritoneal Mesothelioma

Further Study Details:

OBJECTIVES:

  • Determine the objective tumor response rate in chemotherapy-naïve patients with malignant pleural mesothelioma treated with pemetrexed disodium and gemcitabine.

  • Determine the median survival of patients with malignant pleural or peritoneal mesothelioma treated with this regimen.

  • Determine the time to objective tumor response and duration of response in patients treated with this regimen.

  • Determine the time to treatment failure in patients treated with this regimen.

  • Determine the time to progressive disease in patients treated with this regimen.

  • Determine the progression-free and overall survival of patients treated with this regimen.

  • Determine the quantitative and qualitative toxic effects of this regimen in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and pemetrexed disodium IV over 8-15 minutes on day 8. Treatment repeats every 21 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 30 days and then every 3 months.

PROJECTED ACCRUAL: A total of 18-73 patients will be accrued for this study.

Eligibility

Ages Eligible for Study: 18 Years and above, Genders Eligible for Study: Both

Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed malignant pleural or peritoneal mesothelioma of 1 of the following subtypes:

  • Epithelial

  • Sarcomatoid

  • Mixed subtype

  • Disease not amenable to curative surgery

  • Measurable disease

  • At least 1 measurable lesion at least 20 mm by conventional techniques or at least 10 mm by spiral CT scan

  • At least 1 level on lesion scan must have 1 pleural rind measurement at least 15 mm

  • If there is only 1 measurable lesion, the neoplastic nature must be histologically confirmed

  • Clinically detected lesions are only considered measurable if superficial (e.g., skin nodules and palpable lymph nodes)

  • The following are not considered measurable disease:

  • Pleural effusions

  • Positive bone scans

  • No known or suspected brain metastases

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • At least 12 weeks

Hematopoietic

  • Absolute neutrophil count at least 1,500/mm^3

  • Platelet count at least 100,000/mm^3

  • Hemoglobin at least 9 g/dL

Hepatic

  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)

  • Alkaline phosphatase no greater than 3 times ULN*

  • ALT and AST no greater than 3 times ULN*

  • Albumin at least 2.5 g/dL NOTE: *No greater than 5 times ULN in the case of liver involvement by tumor

Renal

  • Creatinine clearance at least 45 mL/min

Other

  • Not pregnant or nursing

  • Negative pregnancy test

  • Fertile patients must use effective contraception during and for 3 months after study participation

  • No active infection

  • No concurrent serious systemic disorders (including oncologic emergencies) that would preclude study participation

  • No other currently active malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix (patients with previously treated malignancy are eligible if at less than 30% risk of relapse)

  • Able to tolerate folic acid or cyanocobalamin administration

PRIOR CONCURRENT THERAPY

Biologic therapy

  • No prior intracavitary immunomodulators, unless given for pleurodesis

  • No filgrastim (G-CSF) within 24 hours of study chemotherapy administration

  • No concurrent immunotherapy

  • No concurrent routine colony-stimulating factor therapy

  • No concurrent stimulators of thrombopoiesis

Chemotherapy

  • No prior systemic chemotherapy

  • No other concurrent chemotherapy

Endocrine therapy

  • No concurrent hormonal therapy for cancer

Radiotherapy

  • Prior radiotherapy to the target lesion allowed provided the lesion has clearly progressed

  • At least 4 weeks since prior radiotherapy

  • No concurrent non-palliative radiotherapy

Surgery

  • No concurrent surgery for cancer

Other

  • At least 2 weeks since prior pleurodesis

  • No prior intracavitary cytotoxic drugs, unless given for pleurodesis

  • More than 4 weeks since prior investigational agents

  • No aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) within 2 days of pemetrexed disodium administration

  • No long-acting NSAIDs (e.g., naproxen, piroxicam, diflunisal, nabumetone, rofecoxib, or celecoxib) within 5 days of pemetrexed disodium administration

  • No other concurrent experimental medications (except thymidine)

Location and Contact Information

Ohio
Ireland Cancer Center, Cleveland, Ohio, 44106-5065, United States; Recruiting
Afshin Dowlati, MD 216-844-1228

Study chairs or principal investigators
Afshin Dowlati, MD, Study Chair, Ireland Cancer Center

*** POSTED SEPTEMBER 2003 ***