Polyglutamate Camptothecin in Treating Patients With Advanced Cancer

Phase I Study of CT-2106 in Patients With Advanced Malignancy

RATIONALE: Drugs used in chemotherapy such as polyglutamate camptothecin may be able to deliver the drug directly to tumor cells while leaving normal cells undamaged.

PURPOSE: Phase I trial to study the effectiveness of polyglutamate camptothecin in treating patients who have advanced cancer.

OBJECTIVES:

• Determine the maximum tolerated dose of polyglutamate camptothecin (CT-2106) in patients with advanced malignancies.
• Determine the tolerability of this drug in these patients.
• Determine the safety of this drug in these patients.
• Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.
• Determine the disease response in patients treated with this drug.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive polyglutamate camptothecin (CT-2106) IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients receive 2 additional courses beyond confirmation of complete response.

Cohorts of 3-6 patients receive escalating doses of CT-2106 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 3 weeks.

PROJECTED ACCRUAL: A total of 12-48 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced malignancy
• No active brain metastases (as indicated by clinical symptoms, cerebral edema, or progressive tumor growth) that have been unstable for at least 8 weeks

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)
• AST and ALT no greater than 2.5 times ULN (5 times ULN if liver metastases are present)

Renal

• Creatinine no greater than 1.5 times ULN
• No history of hemorrhagic cystitis
• No history of microscopic hematuria associated with drug therapy or radiotherapy or of unknown origin

Cardiovascular

• No significant cardiac disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to comply with study schedule and assessments
• No other significant nonmalignant systemic disease
• No active infection
• No other condition that would in the investigator's opinion make the patient an inappropriate study candidate

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No more than 3 prior chemotherapy regimens
• More than 4 weeks since prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior definitive radiotherapy (except for palliative reasons to sites of nonmeasurable disease, in patients with measurable disease at baseline)
• Concurrent palliative radiotherapy allowed

Surgery

• More than 4 weeks since prior major thoracic or abdominal surgery

Other

• Recovered from prior therapy (except alopecia or stable grade 1 neuropathy)
• More than 4 weeks since prior investigational agents
• No prior myeloablative therapy