Irinotecan in Treating Children With Refractory or Progressive Solid Tumors

Unspecified Childhood Solid Tumor, Protocol Specific Clinical Trial

Official title:

Pediatric Phase I and Pharmacokinetic Study of Irinotecan

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00016861
• Other study ID #: TCCC-H-6957
• Secondary ID: CDR0000068568TCC
• Status: Completed
• Phase: Phase 1
• First received: June 6, 2001
• Last updated: June 25, 2013
• Start date: September 1998
• Est. completion date: January 2005

Study information

• Verified date: November 2004
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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 who have refractory or progressive solid tumors.

Description:

OBJECTIVES:

• Determine the maximum tolerated dose and dose-limiting toxicity of irinotecan in children with refractory or progressive solid tumors.

• 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.

• Determine the benefit this drug offers this patient population.

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: January 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 21 Years

Eligibility

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

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/mm^3

• Platelet count at least 100,000/mm^3

• 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

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)

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Unspecified Childhood Solid Tumor, Protocol Specific

Intervention

Drug:
• irinotecan hydrochloride

Locations

Country	Name	City	State
United States	Texas Children's Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Texas Children's Cancer Center

Country where clinical trial is conducted

United States,