Irinotecan in Treating Children With Refractory or Advanced Solid Tumors Who Are Receiving Anticonvulsants

Children's Oncology Group

Status and phase: Completed; Phase 1

Conditions: Unspecified Childhood Solid Tumor, Protocol Specific

Treatments: Drug: irinotecan hydrochloride

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00008424

POG-P9871 (Other Identifier)

P9871

CDR0000068410 (Other Identifier)

COG-P9871 (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.

PURPOSE: Phase I trial to study the effectiveness of irinotecan in treating children with refractory or advanced solid tumors who are receiving anticonvulsants.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose of irinotecan in children with refractory or advanced solid tumors receiving anticonvulsants.
• Determine the dose-limiting toxicity of irinotecan in this patient population.
• Evaluate the pharmacokinetic behavior of this treatment regimen in these patients.
• Determine, preliminarily, the antitumor activity of this treatment regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to type of concurrent anticonvulsant (enzyme activating anticonvulsants vs valproic acid vs other anticonvulsants).

Patients receive irinotecan IV over 1 hour daily for 5 days. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of irinotecan 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 up to 4 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 3-25 patients will be accrued for this study.

Enrollment: 7 patients

Sex: All

Ages: 1 to 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed malignancy refractory to conventional therapy or for which no conventional therapy exists

  • Histologic confirmation not required for brain stem tumors

• Concurrently on anticonvulsants at a steady level for at least 2 weeks

PATIENT CHARACTERISTICS:

Age:

• 1-21 years old

Performance status:

• Karnofsky 50-100% (over 10 years of age)
• Lansky 50-100% (10 years of age or under)

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Neutrophil count at least 1,000/mm3
• Platelet count at least 100,000/mm3 (transfusion independent)
• Hemoglobin at least 8.0 g/dL (red blood cell transfusions allowed)

Hepatic:

• Bilirubin no greater than 1.5 times normal for age
• SGPT less than 5 times normal for age
• Albumin at least 2 g/dL

Renal:

• Creatinine no greater than 1.5 times normal for age OR
• Creatinine clearance or radioisotope glomerular filtration rate at least lower limit of normal for age

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection
• No evidence of active graft-vs-host disease
• Neurologic deficits for CNS tumors stable for at least 2 weeks prior to study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 1 week since prior antineoplastic biologic therapy
• At least 6 months since prior allogeneic stem cell transplantation
• At least 1 week since prior growth factors
• No concurrent sargramostim (GM-CSF)
• No concurrent prophylactic growth factors during first course of study therapy
• Recovered from prior immunotherapy

Chemotherapy:

• At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosourea) and recovered

Endocrine therapy:

• Concurrent dexamethasone for CNS tumors with increased intracranial pressure allowed if dose stable or decreasing for at least 2 weeks prior to study

Radiotherapy:

• At least 2 weeks since prior local palliative radiotherapy (small part)
• At least 6 months since prior craniospinal radiotherapy
• At least 6 months since prior radiotherapy to at least 50% of pelvis
• At least 6 weeks since prior substantial bone marrow radiotherapy
• Recovered from prior radiotherapy

Surgery:

• Not specified

Other:

• No other concurrent investigational agent