Pediatric Phase I and Pharmacokinetic Study of Irinotecan
1 Year
21 Years
Both
Unspecified Childhood Solid Tumor, Protocol Specific
Trial Information
Pediatric Phase I and Pharmacokinetic Study of Irinotecan
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.
Inclusion 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
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)
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Susan M. Blaney, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Texas Children's Cancer Center
Authority:
United States: Federal Government
Study ID:
TCCC-H-6957
NCT ID:
NCT00016861
Start Date:
September 1998
Completion Date:
January 2005
Related Keywords:
- Unspecified Childhood Solid Tumor, Protocol Specific
- unspecified childhood solid tumor, protocol specific
- Neoplasms
Name | Location |
|---|---|
| Texas Children's Cancer Center | Houston, Texas 77030-2399 |
