RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die.
PURPOSE: Phase I trial to study the effectiveness of oxaliplatin in treating children who
have advanced solid tumors.
- Determine the maximum tolerated dose of oxaliplatin in children with advanced solid
- Determine the toxic effects of this drug in these patients.
- Determine the safety of this drug in these patients.
- Determine the pharmacokinetics of this drug in these patients.
- Assess the relationship between pharmacokinetic parameters and toxicity of this regimen
and response in these patients.
- Determine the anti-tumor effects of this drug in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive oxaliplatin IV over 2 hours on day 1 (every 3 weeks for up to 6 courses) OR
on days 1, 14, and 28 (every 6 weeks for up to 3 courses). Treatment continues in the
absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of oxaliplatin until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2
of 3 or 2 of 6 patients experience dose-limiting toxicity.
Once the MTD for dose levels 1-4 is determined, an additional cohort of 3-6 patients is
accrued and treated with oxaliplatin as above every 2 weeks (for up to 9 doses).
PROJECTED ACCRUAL: Approximately 6-20 patients will be accrued for this study within 1-3.3
- Histologically confirmed metastatic or unresectable solid tumors that are not
amenable to standard treatment
- Histological confirmation not required for brain stem tumors
- No known brain metastases
- No leukemia
- 21 and under
- ECOG 0-2 OR
- Lansky 50-100%
- Not specified
- Absolute neutrophil count at least 1,000/mm^3 (except with marrow involvement)
- Hemoglobin at least 8 g/dL
- Platelet count at least 100,000/mm^3
- Bilirubin 0.2-1.4 mg/dL
- AST/ALT no greater than 3 times upper limit of normal
- Creatinine normal for age OR
- Creatinine clearance at least 50 mL/min
- Electrolytes, calcium, and phosphorus normal
- No symptomatic congestive heart failure, unstable angina, or cardiac arrhythmia
- Not pregnant or nursing
- Fertile patients must use effective contraception
- HIV negative
- No active graft-vs-host disease (GVHD)
- No allergy to platinum compounds or antiemetics
- No uncontrolled concurrent illness or infection
- No evidence of neuropathy
- Blood sugar normal
PRIOR CONCURRENT THERAPY:
- At least 1 week since prior hematopoietic growth factors
- At least 3 months since prior stem cell transplantation and recovered
- At least 3 weeks since prior chemotherapy (6 weeks for nitrosourea)
- Not specified
- At least 6 weeks since prior extensive radiotherapy to significant marrow-containing
- At least 6 months since prior craniospinal radiotherapy; total abdominal, pelvic, or
extensive lung radiotherapy; or mantle and Y-port radiotherapy
- At least 6 months since prior total body irradiation
- Not specified
- No concurrent therapy for GVHD
- No other concurrent anticancer investigational or commercial agents
- No other concurrent anticancer therapy