Combination Chemotherapy in Treating Children With Solid Tumors That Have Not Responded to Previous Therapy

Children's Oncology Group

Status and phase: Completed; Phase 1

Conditions: Unspecified Childhood Solid Tumor, Protocol Specific

Treatments: Drug: irinotecan hydrochloride; Drug: vincristine sulfate

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00006095

CCG-P9971 (Other Identifier)

P9971

CDR0000068102 (Other Identifier)

POG-9971 (Other Identifier)

COG-P9971 (Other Identifier)

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. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of vincristine plus irinotecan in treating children who have solid tumors that have not responded to previous therapy.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose and dose limiting toxicity of vincristine when administered in combination with irinotecan in children with refractory solid tumors.
• Determine the safe and tolerable phase II dose of this combination regimen in this patient population.
• Determine the pharmacokinetics of this combination regimen in these patients.
• Determine the incidence and severity of other toxicities of this combination regimen in these patients.
• Determine preliminary evidence of antitumor activity of this combination regimen in this patient population.

OUTLINE: This is a dose-escalation study of vincristine.

Patients receive vincristine IV on day 2 of the first course (day 1 of subsequent courses) and days 8, 15, 22, and 29, and irinotecan IV over 1 hour on days 1-5 and 22-26. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients with responsive or stable disease receive additional courses of therapy for a maximum of 1 year.

Cohorts of 3-6 patients receive escalating doses of vincristine until the maximum tolerated dose (MTD) is reached. 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 every 6 months for 4 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 3-12 patients will be accrued for this study within 1 year.

Enrollment: 20 patients

Sex: All

Ages: 1 to 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed initial diagnosis of malignant solid tumor refractory to conventional therapy or for which no effective therapy exists

  • Brain tumors allowed if not on anticonvulsants
  • Brainstem gliomas allowed without histologic diagnosis
  • Solid lymphomas allowed

• No bone marrow involvement

PATIENT CHARACTERISTICS:

Age:

• 1 to 21

Performance status:

• Karnofsky 50-100% if over 10 years of age
• Lansky 50-100% if 10 years of age and under

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 8 g/dL (transfusion allowed)

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• ALT less than 5 times normal
• Albumin at least 2 g/dL

Renal:

• Creatinine normal for age OR
• Glomerular filtration rate normal for age

Other:

• No uncontrolled infection
• No other significant systemic illness
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 1 week since prior biologic therapy and recovered
• At least 1 week since prior growth factors
• No prior stem cell transplantation

Chemotherapy:

• At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
• No more than 2 prior chemotherapy regimens
• No other concurrent cancer chemotherapy

Endocrine therapy:

• Concurrent dexamethasone allowed in patients with CNS tumors provided dose is stable or decreasing for at least 2 weeks prior to study

Radiotherapy:

• Recovered from prior radiotherapy
• At least 2 weeks since prior local palliative radiotherapy (small port)
• No prior substantial bone marrow radiotherapy
• No prior central axis radiotherapy
• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• No concurrent anticonvulsants
• No other concurrent anticancer therapy or investigational agents

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

Vincristine Sulfate 1.5 mg/m2/wk and Irinotecan

Experimental group

Treatment:

Drug: vincristine sulfate

Drug: irinotecan hydrochloride

Vincristine sulfate 2.0 mg/m2/wk and Irinotecan

Experimental group

Treatment:

Drug: vincristine sulfate

Drug: irinotecan hydrochloride