RATIONALE: Endostatin may stop the growth of solid tumors by stopping blood flow to the
PURPOSE: Phase I trial to study the effectiveness of endostatin in treating patients who
have advanced refractory solid tumors.
OBJECTIVES: I. Determine the maximum tolerated dose (MTD) and Phase II dose of endostatin in
patients with advanced refractory solid tumors. II. Determine the qualitative and
quantitative nature of the toxicities encountered with endostatin in this patient
population. III. Evaluate the basic pharmacokinetics and metabolism of endostatin by
measurement of plasma levels by EIA and mass spectrometry in this patient population. IV.
Investigate the relationship between pharmacokinetic parameters and toxicity in this patient
population. V. Evaluate biologic evidence of angiogenesis inhibition in patients receiving
OUTLINE: This is a dose escalation study. Patients receive endostatin IV over 1 hour daily
for 28 days, followed by 1 week of rest. Patients receive subsequent courses of daily
therapy in the absence of disease progression or unacceptable toxicity. Cohorts of 3
patients receive escalating doses of endostatin 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 toxicities.
PROJECTED ACCRUAL: Approximately 30-40 patients will be accrued for this study.
DISEASE CHARACTERISTICS: Histologically confirmed advanced refractory solid tumor for
which no curative therapy exists Bidimensionally measurable or evaluable disease
accessible to biopsy No brain metastases or primary brain tumors
PATIENT CHARACTERISTICS: Age: Over 18 Performance status: ECOG 0-1 Life expectancy: Not
specified Hematopoietic: WBC at least 4,000/mm3 OR Absolute neutrophil count at least
2,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin normal AST/SGOT no
greater than 2 times upper limit of normal (ULN) Renal: Creatinine no greater than 1.5
mg/dL OR Creatinine clearance greater than 60 mL/min Other: No serious active infection
Not pregnant or nursing Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 4 weeks
since prior chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 4 weeks
since prior radiotherapy and recovered Surgery: Not specified