Phase II Study of Ecteinascidin 743 in Patients With Unresectable Malignant Mesothelioma

OBJECTIVES

I. Determine partial and complete response rates in patients with unresectable malignant mesothelioma treated with ecteinascidin 743.

II. Determine the toxicity profile of this drug in these patients.

III. Determine the pharmacokinetic/pharmacodynamic relationships of this drug in these patients.

IV. Determine the duration of response, time to disease progression, 6-month progression-free survival, time to treatment failure, and overall survival of patients treated with this drug.

V. Assess the quality of life of these patients treated with this drug.

ENTRY CRITERIA

--Disease Characteristics--

• Histologically or cytologically confirmed malignant mesothelioma that is not amenable to curative surgery
• At least 1 unidimensionally measurable lesion that is at least 15 mm by CT scan

OR

• At least 1 bidimensionally measurable lesion that is at least 10 mm by CT scan
• Lesions in previously irradiated area are not considered measurable unless there is evidence of progression
• No symptomatic brain or leptomeningeal involvement

--Prior/Concurrent Therapy--

Biologic therapy

• No prophylactic hematopoietic colony-stimulating factors (e.g., filgrastim (G-CSF) or sargramostim (GM-CSF))
• Chemotherapy
• No prior systemic chemotherapy including intracavity chemotherapy unless administered for pleurodesis
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy

Radiotherapy

• See Disease Characteristics
• At least 30 days since prior radiotherapy and recovered
• No concurrent radiotherapy except palliative local radiotherapy to non-target lesions

Surgery

• See Disease Characteristics

At least 14 days since prior pleurodesis Recovered from prior surgery

Other

• At least 30 days since prior participation in another therapeutic clinical trial or therapy with other investigational drugs No concurrent treatment for other neoplastic disease No other concurrent experimental anticancer medication

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-1 OR
• Karnofsky 70-100%
• Life expectancy: At least 3 months

Hematopoietic

• 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 upper limit of normal (ULN)
• Alkaline phosphatase no greater than ULN unless bone metastases is present
• AST/ALT no greater than 2.5 times ULN
• Albumin at least 2.5 g/dL
• No chronic active liver disease

Renal

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 40 mL/min

Cardiovascular

• No uncontrolled heart disease
• No uncontrolled hypertension

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and one month after study
• No other serious illness or medical condition
• No history of significant neurological or psychiatric disorders
• No significant active infection
• No other concurrent neoplastic disease except non-melanoma skin cancer or carcinoma in situ of the cervix

OUTLINE

This is a multicenter study.

Patients receive ecteinascidin 743 IV over 3 hours on day 1. Treatment repeats every 3 weeks for at least 6 courses in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) receive 2 additional courses after achieving CR.

Quality of life is assessed at baseline and at the beginning of each course of therapy.

Patients are followed every 3 months.

STRATIFICATION

Not abstracted

SPECIAL STUDY PARAMETERS

Not abstracted

END POINTS

Not abstracted

PROJECTED ACCRUAL

A total of 20-36 patients will be accrued for this study within 12-24 months.

WARNING

The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.

DOSAGE SCHEDULE

Not abstracted

DOSAGE FORMS

Not abstracted

PARTICIPATING ORGANIZATIONS/STUDY CONTACTS

Lee M. Krug, Chair Ph212-639-8420
Memorial Sloan-Kettering Cancer Center

STUDY CONTACTS

Massachusetts
Aaron Deykin, Phone: 617-732-5499
Brigham and Women's Hospital
Boston, Massachusetts, U.S.A.

Bruce Johnson, Phone: 617-632-4790
Dana-Farber Cancer Institute
Boston, Massachusetts, U.S.A.

Jeffrey G. Supko, Phone: 617-724-1970
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, U.S.A.

New York
Lee M. Krug, Phone: 212-639-8420
Memorial Sloan-Kettering Cancer Center
New York, New York, U.S.A.

*** POSTED ON FEBRUARY 13, 2002 ***