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.
- 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.
- 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
- 18 and over
- ECOG 0-2
- At least 12 weeks
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 9 g/dL
- 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
- 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
- No significant cardiac disease
- 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:
- Not specified
- No more than 3 prior chemotherapy regimens
- More than 4 weeks since prior chemotherapy
- Not specified
- 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
- More than 4 weeks since prior major thoracic or abdominal surgery
- Recovered from prior therapy (except alopecia or stable grade 1 neuropathy)
- More than 4 weeks since prior investigational agents
- No prior myeloablative therapy