Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Cisplatin With or Without Raltitrexed in Treating Patients With Malignant Mesothelioma of the Pleura

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed Over 18 Other EORTC-08983 NCT00004920

Objectives

1. Compare overall survival in patients with malignant pleural mesothelioma treated with raltitrexed with or without cisplatin.
2. Assess toxicity, progression free survival, and quality of life with these treatment regimens in these patients.
3. Evaluate objective response and duration of response to these treatment regimens in patients with measurable disease.

Entry Criteria

Disease Characteristics:

• Histologically confirmed malignant pleural mesothelioma



• No CNS metastases

Prior/Concurrent Therapy:

Biologic therapy:

• No concurrent immunotherapy before first disease progression

Chemotherapy:

• No prior systemic or intracavitary cytotoxic chemotherapy
• No other prior or concurrent chemotherapy before first disease progression
• No prior or concurrent pleurodesis with cytotoxic drugs (e.g., bleomycin)

Endocrine therapy:

• No concurrent hormonal therapy except corticosteroids before first disease progression

Radiotherapy:

• At least 4 weeks since prior radiotherapy to target lesion and progression observed
• Concurrent palliative radiotherapy to painful lesions allowed only if target lesion outside of irradiated field

Surgery:

• Prior surgery allowed if followed by disease progression

Other:

• At least 1 month since prior investigational drugs

Patient Characteristics:

Age:

• Over 18

Performance status:

• ZUBROD, ECOG, WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Hemoglobin at least 10.0 g/dL
• WBC at least 4,000/mm³
• Absolute neutrophil count at least 2,000/mm³
• Platelet count at least 100,000/mm³

Hepatic:

• Bilirubin less than 1.46 mg/dL
• Albumin at least 3.0 g/dL
• ALAT/ASAT less than 2.5 times upper limit of normal (ULN) (less than 5 times ULN if liver involvement)

Renal:

• Creatinine less than 1.69 mg/dL
• Creatinine clearance at least 65 mL/min

Cardiovascular:

• Not specified

Pulmonary:

• Not specified

Other:

• No other prior or concurrent malignancies within past 5 years except adequately treated carcinoma in situ of the cervix or basal or squamous cell carcinoma of the skin
• No prior malignant melanoma, hypernephroma or breast carcinoma
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study
• No uncontrolled infections
• No psychological, familial, sociological, or geographical condition that precludes study compliance

Expected Enrollment

A total of 240 patients will be accrued for this study over 24 months.

Outline

This is a randomized, open, multicenter study. Patients are stratified according to performance status (0 vs 1-2) and WBC count (less than 8,300/mm3 vs 8,300/mm3 or more). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive cisplatin IV over 1-2 hours on day 1.



• Arm II: Patients receive raltitrexed IV over 15 minutes followed by cisplatin IV over 1-2 hours on day 1.

Treatment continues every 3 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed before study, prior to each course, after the last course, and then every 6 weeks for 1 year.

Patients are followed every 6 weeks until death.

Bottomley A, Coens C, Efficace F, et al.: Symptoms and patient-reported well-being: do they predict survival in malignant pleural mesothelioma? A prognostic factor analysis of EORTC-NCIC 08983: randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma. J Clin Oncol 25 (36): 5770-6, 2007.[PUBMED Abstract]

Bottomley A, Gaafa R, Manegold C, et al.: Short-term treatment-related symptoms and quality of life: results from an international randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an EORTC Lung-Cancer Group and National Cancer Institute, Canada, Intergroup Study. J Clin Oncol 24 (9): 1435-42, 2006.[PUBMED Abstract]

van Meerbeeck JP, Gaafar R, Manegold C, et al.: Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada. J Clin Oncol 23 (28): 6881-9, 2005.[PUBMED Abstract]

Van Meerbeeck JP, Manegold C, Gaafar R, et al.: A randomized phase III study of cisplatin with or without raltitrexed in patients (pts) with malignant pleural mesothelioma (MPM): an intergroup study of the EORTC Lung Cancer Group and NCIC. [Abstract] J Clin Oncol 22 (Suppl 14): A-7021, 622s, 2004.

Francart J, Legrand C, Sylvester R, et al.: Progression-free survival rate as primary end point for phase II cancer clinical trials: application to mesothelioma--The EORTC Lung Cancer Group. J Clin Oncol 24 (19): 3007-12, 2006.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Jan Van Meerbeeck, MD, PhD, Protocol chair(Contact information may not be current)		Ph: 31-10-463-9222

Registry Information
Official Title		Phase III Study of Tomudex and Cisplatin Versus Cisplatin in Malignant Pleural Mesothelioma
Trial Start Date		1999-11-26
Registered in ClinicalTrials.gov		NCT00004920
Date Submitted to PDQ		2000-01-13
Information Last Verified		2001-05-07