Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Irinotecan in Treating Children With Refractory or Progressive Solid Tumors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	1 to 21	Other	TCCC-H-6957 TCCC-GCRC-0654, NCI-V01-1654, NCT00016861

Objectives

1. Determine the maximum tolerated dose and dose-limiting toxicity of irinotecan in children with refractory or progressive solid tumors.
2. Determine the pharmacokinetics of this drug and its metabolites (SN-38, SN-38G, and APC) administered with and without concurrent anticonvulsants in this patient population.
3. Determine the benefit this drug offers this patient population.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed solid tumor refractory to standard therapy or for which no known effective therapy exists
  • Brain tumors eligible
    • Histologic verification waived for brain stem gliomas



• Evaluable disease



• No bone marrow involvement

Prior/Concurrent Therapy:

Biologic therapy:

• At least 6 months since prior autologous bone marrow transplantation (BMT) (not including stem cell rescue after high-dose chemotherapy)
• At least 1 week since prior growth factors
• No prior BMT with total body irradiation (stratum I)
• No prior BMT with or without total body irradiation (stratum 2)
• No prior allogeneic BMT (all strata)
• No concurrent sargramostim (GM-CSF)
• No other concurrent prophylactic growth factor support during the first course of therapy

Chemotherapy:

• At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)
• No prior irinotecan
• No more than 2 prior multi-agent chemotherapy regimens (stratum 2)
• No other concurrent chemotherapy

Endocrine therapy:

• Concurrent dexamethasone allowed if on stable or decreasing dose for at least 2 weeks prior to study

Radiotherapy:

• At least 6 months since prior craniospinal radiotherapy or radiotherapy to 50% or more of the pelvis
• At least 6 weeks since other prior substantial bone marrow radiotherapy
• No prior central axis radiotherapy, pelvic radiotherapy, and/or total abdominal radiotherapy (stratum 2)

Surgery:

• Not specified

Other:

• Recovered from all prior therapy
• No other concurrent investigational agents
• Concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, phenobarbital, carbamazepine) allowed if on stable dose for at least 2 weeks prior to study (stratum 3)
• Concurrent valproic acid allowed if combined with another enzyme inducing anticonvulsant drug (stratum 3)

Patient Characteristics:

Age:

• 1 to 21

Performance status:

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

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• Hemoglobin at least 8 g/dL

Hepatic:

• Bilirubin less than 1.5 mg/dL
• SGPT less than 5 times normal

Renal:

• Creatinine normal

  OR

• Glomerular filtration rate at least 70 mL/min

Other:

• No uncontrolled infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study

Expected Enrollment

Approximately 20-25 patients will be accrued for this study.

Outline

This is a dose-escalation, multicenter study. Patients are accrued into stratum 1 initially and into stratum 2 if stratum 1 closes due to dose-limiting toxicity of myelosuppression or diarrhea. Patients on anticonvulsants will be accrued into stratum 3 and must meet the eligibility criteria for the stratum that is open (stratum 1 or stratum 2). (Stratum 1 closed as of 2002-09-15).

Patients receive irinotecan IV over 90 minutes weekly for 4 weeks. Treatment repeats every 6 weeks 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) with and without anticonvulsants is determined. The MTD is defined as the dose preceding that at which 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.

Trial Contact Information

Trial Lead Organizations

Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital

Susan Blaney, MD, Protocol chair		Ph: 832-822-1482 Email: sblaney@txccc.org

Registry Information
Official Title		Pediatric Phase I and Pharmacokinetic Study of Irinotecan
Trial Start Date		1998-09-08
Registered in ClinicalTrials.gov		NCT00016861
Date Submitted to PDQ		2001-02-28
Information Last Verified		2004-11-08

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