Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Cisplatin With or Without Pemetrexed Disodium in Treating Patients With Malignant Mesothelioma of the Pleura That Cannot be Removed by Surgery

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Completed 18 and over NCI, Pharmaceutical / Industry MSKCC-99085 CWRU-LILY-1599, LILLY-H3E-MC-JMCH(a), NCI-G00-1767, NCT00005636

Objectives

I.  Compare survival in patients with malignant pleural mesothelioma when 
treated with cisplatin with or without LY231514.

II.  Compare duration of response, time to progression, and time to treatment 
failure in these patients with these treatment regimens.

III.  Compare tumor response rate and clinical benefit of these treatment 
regimens in these patients.

IV.  Compare Lung Cancer Symptom Scale scores, pulmonary function test scores, 
and lung density determinations with these treatment regimens in these 
patients.

V.  Compare toxicity of these treatment regimens in these patients.

VI.  Assess pharmacokinetics and vitamin metabolite status with these 
treatment regimens in these patients.

Entry Criteria

Disease Characteristics:

Histologically confirmed malignant mesothelioma of the pleura not amenable to
curative surgery
 Must be radiologically accessible

Unidimensionally or bidimensionally measurable disease
 Pleural effusions or positive bone scan not considered measurable

No brain metastases

Prior/Concurrent Therapy:

Biologic therapy:
 Prior immunomodulators allowed for pleurodesis 
 No concurrent immunotherapy

Chemotherapy:
 No prior systemic chemotherapy
 At least 1 week since prior bleomycin for pleurodesis
 Prior intracavitary cytotoxic drugs allowed for pleurodesis
 No other concurrent chemotherapy

Endocrine therapy:
 No concurrent hormonal anticancer therapy

Radiotherapy:
 At least 4 weeks since prior radiotherapy to target lesion
  Lesion must be clearly progressive
 No concurrent radiotherapy

Surgery:
 See Disease Characteristics
 No concurrent surgery for cancer

Other:
 At least 4 weeks since any other prior investigational agent 
 No concurrent aspirin or other nonsteroidal antiinflammatory drug from 2 days
  prior to 2 days after study (5 days prior for long acting agents such as
  piroxicam, naproxen, diflunisal, or nabumetone)
 No other concurrent experimental medications
 

Patient Characteristics:

Age:
 18 and over

Performance status:
 Karnofsky 70-100%

Life expectancy:
 At least 12 weeks

Hematopoietic:
 Absolute neutrophil count at least 1,500/mm3
 Platelet count at least 100,000/mm3
 Hemoglobin at least 9 g/dL

Hepatic:
 Bilirubin no greater than 1.5 times upper limit of normal (ULN)
 Alkaline phosphatase, AST, and ALT no greater than 3.0 times ULN (no greater
  than 5 times ULN with liver involvement)
 Albumin at least 3.0 g/dL

Renal:
 Creatinine clearance at least 45 mL/min

Other:
 No serious systemic disorders that may preclude study
 No prior primary malignancy within the past 5 years except carcinoma in situ
  of the cervix or adequately treated basal cell carcinoma of the skin  
 No obvious malnourishment or greater than 10% weight loss within 6 weeks
  prior to study
 No active infection
 Not pregnant or nursing
 Fertile patients must use effective contraception during and for 3 months
  after study

Expected Enrollment

A total of 280 patients (140 per treatment arm) will be accrued for this study 
within 15 months.

Outline

This is a randomized, single blind, multicenter study.  Patients are 
stratified according to performance status (Karnofsky 70-80% vs 90-100%), 
degree of measurability (bidimensional vs unidimensional only), histologic 
subtype (epithelial vs all others), WBC (8,300/mm3 and higher vs less than 
8,300/mm3), pain intensity (low vs high), analgesic consumption (low vs high), 
dyspnea (low vs high), homocysteine (low vs high), gender, country, and 
treatment center.  Patients are randomized to one of two treatment arms.

Arm I:  Patients receive LY231514 IV over 10 minutes followed by cisplatin IV 
over 2 hours on day 1.

Arm II:  Patients receive cisplatin as in arm I.

Treatment repeats every 21 days for at least 6 courses in the absence of 
disease progression or unacceptable toxicity.

Patients are followed at 4 weeks, and then every 3 months thereafter.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

David Ilson, MD, PhD, Protocol chair		Ph: 212-639-8306; 800-525-2225

Registry Information
Official Title		A Single-Blind Randomized Phase III Trial of MTA Plus Cisplatin versus Cisplatin in Patients with Malignant Pleural Mesothelioma
Trial Start Date		1999-11-23
Registered in ClinicalTrials.gov		NCT00005636
Date Submitted to PDQ		2000-03-15
Information Last Verified		2007-06-12
NCI Grant/Contract Number		CA08748