Irinotecan in Treating Children With Refractory or Progressive Solid Tumors

NCT ID: NCT00016861

Last Updated: 2013-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-09-30
• Study Completion Date: 2005-01-31

Brief 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.

Detailed 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.

Conditions

Unspecified Childhood Solid Tumor, Protocol Specific

Study Design

• Primary Study Purpose: TREATMENT

Interventions

irinotecan hydrochloride

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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)

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Texas Children's Cancer Center

OTHER

Sponsor Role: lead

Principal Investigators

Susan M. Blaney, MD

Role: STUDY_CHAIR

Texas Children's Cancer Center

Locations

Texas Children's Cancer Center

Houston, Texas, United States

Countries

United States

Other Identifiers

CDR0000068568

Identifier Type: REGISTRY

Identifier Source: secondary_id

TCCC-GCRC-0654

Identifier Type: -

Identifier Source: secondary_id

NCI-V01-1654

Identifier Type: -

Identifier Source: secondary_id

TCCC-H-6957

Identifier Type: -

Identifier Source: org_study_id