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

Malignant Mesothelioma Clinical Trial

Official title:

Phase III Study of Tomudex and Cisplatin Versus Cisplatin in Malignant Pleural Mesothelioma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004920
• Other study ID #: EORTC-08983
• Secondary ID: EORTC-08983
• Status: Completed
• Phase: Phase 3
• First received: March 7, 2000
• Last updated: July 17, 2012
• Start date: November 1999

Study information

• Verified date: July 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether receiving cisplatin with raltitrexed is more effective than cisplatin alone for malignant mesothelioma.

PURPOSE: Randomized phase III trial to compare the effectiveness of cisplatin with or without raltitrexed in treating patients who have malignant mesothelioma of the pleura.

Description:

OBJECTIVES:

• Compare overall survival in patients with malignant pleural mesothelioma treated with raltitrexed with or without cisplatin.

• Assess toxicity, progression free survival, and quality of life with these treatment regimens in these patients.

• Evaluate objective response and duration of response to these treatment regimens in patients with measurable disease.

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 256
• Est. primary completion date: January 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant pleural mesothelioma

• No CNS metastases

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/mm^3

• Absolute neutrophil count at least 2,000/mm^3

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

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

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lung Neoplasms
• Malignant Mesothelioma
• Mesothelioma

Intervention

Drug:
• cisplatin

• raltitrexed

Locations

Country	Name	City	State
Belgium	U.Z. Gasthuisberg	Leuven
Canada	Cancer Care Ontario-Hamilton Regional Cancer Centre	Hamilton	Ontario
Canada	Cancer Care Ontario-London Regional Cancer Centre	London	Ontario
Canada	Trillium Health Centre	Mississauga	Ontario
Canada	McGill University	Montreal	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Princess Margaret Hospital	Toronto	Ontario
Egypt	National Cancer Institute of Egypt	Cairo
France	Assistance Publique Hopitaux de Marseille Hopitaux Sud	Marseille
France	Hopital de la Conception	Marseille
France	Hopital Charles Nicolle	Rouen
Germany	Thoraxklinik Rohrbach	Heidelberg
Italy	Istituto Nazionale per la Ricerca sul Cancro	Genoa (Genova)
Netherlands	University Medical Center Nijmegen	Nijmegen
Netherlands	Erasmus Medical Center	Rotterdam
Netherlands	University Hospital - Rotterdam Dijkzigt	Rotterdam
Netherlands	Academisch Ziekenhuis Utrecht	Utrecht
Peru	Instituto de Enfermedades Neoplasicas	Lima
Poland	Medical University of Gdansk	Gdansk
Poland	Regional Lung Diseases Hospital	Poznan
Switzerland	University Hospital	Basel
Switzerland	Inselspital, Bern	Bern
Switzerland	Kantonsspital - St. Gallen	St. Gallen
United Kingdom	Western General Hospital	Edinburgh	Scotland
United Kingdom	Nottingham City Hospital NHS Trust	Nottingham	England
United Kingdom	Weston Park Hospital	Sheffield	England

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Belgium,  Canada,  Egypt,  France,  Germany,  Italy,  Netherlands,  Peru,  Poland,  Switzerland,  United Kingdom, 

References & Publications (5)

Bottomley A, Coens C, Efficace F, Gaafar R, Manegold C, Burgers S, Vincent M, Legrand C, van Meerbeeck JP; EORTC-NCIC. Symptoms and patient-reported well-being: do they predict survival in malignant pleural mesothelioma? A prognostic factor analysis of EO — View Citation

Bottomley A, Gaafar R, Manegold C, Burgers S, Coens C, Legrand C, Vincent M, Giaccone G, Van Meerbeeck J; EORTC Lung-Cancer Group; National Cancer Institute, Canada. Short-term treatment-related symptoms and quality of life: results from an international — View Citation

Francart J, Legrand C, Sylvester R, Van Glabbeke M, van Meerbeeck JP, Robert A. 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. 2006 Jul 1;24(19):3007-12. — View Citation

van Meerbeeck JP, Gaafar R, Manegold C, Van Klaveren RJ, Van Marck EA, Vincent M, Legrand C, Bottomley A, Debruyne C, Giaccone G; European Organisation for Research and Treatment of Cancer Lung Cancer Group; National Cancer Institute of Canada. Randomized — View Citation

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 Cl