Carboplatin and Irinotecan in Treating Children With Refractory Solid Tumors

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 1

Conditions: Unspecified Childhood Solid Tumor, Protocol Specific

Treatments: Drug: carboplatin; Drug: irinotecan hydrochloride

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT00024284

MSKCC-01071

CNMC-2782

CDR0000068908

BMS-CA124-001

SJCRH-CARCPT

NCI-G01-2016

Details and patient eligibility

About

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 combining carboplatin and irinotecan in treating children who have refractory solid tumors.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose and recommended phase II dose of carboplatin and irinotecan in children with refractory solid tumors.
• Determine the safety profile and dose-limiting toxic effects of this regimen in these patients.
• Determine the pharmacokinetics of this regimen in these patients.
• Determine the preliminary anti-tumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of carboplatin and irinotecan.

Patients receive carboplatin IV over 50 minutes on day 1 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of carboplatin and irinotecan 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.

Patients are followed for at least 30 days.

PROJECTED ACCRUAL: A total of 25-30 patients will be accrued for this study within 6-9 months.

Sex: All

Ages: 1 to 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed solid tumor, including primary brain tumor

  • Progressive disease on standard therapy or for which no standard therapy exists

• No symptomatic brain metastases

PATIENT CHARACTERISTICS:

Age:

• 1 to 21

Performance status:

• Lansky 50-100% (age 10 and under)
• Karnofsky 50-100% (over age 10)

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm3
• Platelet count greater than 100,000/mm3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• ALT no greater than 2.5 times upper limit of normal

Renal:

• Glomerular filtration rate at least 30 mL/min

Other:

• No active infection
• No serious uncontrolled medical disorder
• No psychiatric disorder or other disorder that would preclude study
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 6 months since prior allogeneic bone marrow transplantation without evidence of acute or chronic graft versus host disease
• At least 3 months since prior autologous bone marrow or peripheral blood stem cell transplantation
• At least 4 weeks since prior immunotherapy and recovered
• No concurrent immunotherapy

Chemotherapy:

• No more than 3 prior chemotherapy regimens
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No other concurrent chemotherapy

Endocrine therapy:

• Concurrent hormone replacement therapy or oral contraceptives allowed
• No other concurrent hormonal therapy

Radiotherapy:

• At least 4 weeks since prior radiotherapy (including for brain metastases) and recovered
• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• No other concurrent investigational anticancer drugs
• No other concurrent antitumor therapy
• No concurrent anticonvulsants (e.g., phenytoin, phenobarbital, or carbamazepine) except gabapentin (Neurontin)