Phase I Study of ET-743 in Pediatric Refractory Solid Tumors

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically confirmed malignant solid tumor at original
diagnosis Refractory to standard treatment or no curative therapy available No CNS tumor
No bone marrow metastases (for less heavily pretreated stratum only)

PATIENT CHARACTERISTICS: Age: At least 365 days to 17 years Performance status: Karnofsky
50-100% (for patients older than 10 years) Lansky 50-100% (for patients 10 years and
younger) Life expectancy: At least 8 weeks Hematopoietic: Absolute neutrophil count at
least 1,500/mm3 Platelet count at least 100,000/mm3 (transfusion independent) Hemoglobin
at least 8.0 g/dL (RBC transfusion allowed) Hepatic: Bilirubin no greater than normal SGPT
no greater than 2.5 times normal Albumin at least 2 g/dL Alkaline phosphatase normal Gamma
glutamyl transferase less than 2.5 times normal Renal: Creatinine no greater than 1.5
times normal OR Creatinine clearance or GFR at least lower limit of normal Other: Not
pregnant or nursing Negative pregnancy test Fertile patients must use effective
contraception Creatine phosphokinase less than 2 times normal No uncontrolled infection
Seizure disorder allowed if well controlled on anticonvulsants No CNS toxicity greater
than grade II

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 1 week since prior biologic therapy
and recovered At least 1 week since prior growth factor therapy At least 6 months since
prior peripheral blood stem cell transplantation and no evidence of graft-vs-host disease
For less heavily pretreated stratum: No prior peripheral blood stem cell transplantation
Chemotherapy: At least 4 weeks since prior myelosuppressive chemotherapy (6 weeks for
nitrosoureas) and recovered No prior ecteinascidin 743 For less heavily pretreated
stratum: No more than 2 prior chemotherapy regimens Endocrine therapy: Not specified
Radiotherapy: At least 2 weeks since prior local palliative radiotherapy (small port) At
least 6 weeks since prior substantial bone marrow radiotherapy At least 6 months since
prior craniospinal radiotherapy or radiotherapy to 50% or greater of pelvis For less
heavily pretreated stratum: No prior craniospinal irradiation of 18Gy or greater No prior
irradiation to greater than 50% of pelvis Recovered from toxic effects of prior
radiotherapy Surgery: Not specified Other: No concurrent foods or medication that
interferes with P-450 metabolism Anticonvulsants allowed