Irinotecan in Treating Children With Refractory or Progressive Solid Tumors
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Unspecified Childhood Solid Tumor, Protocol Specific |
Drug: irinotecan hydrochloride |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Primary Purpose: Treatment |
| Official Title: | Pediatric Phase I and Pharmacokinetic Study of Irinotecan |
| Study Start Date: | September 1998 |
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.
Eligibility| Ages Eligible for Study: | 1 Year to 21 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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)
Contacts and Locations| United States, Texas | |
| Texas Children's Cancer Center | |
| Houston, Texas, United States, 77030-2399 | |
| Study Chair: | Susan M. Blaney, MD | Texas Children's Cancer Center |
More Information
Additional Information:
No publications provided
| ClinicalTrials.gov Identifier: | NCT00016861 History of Changes |
| Other Study ID Numbers: | CDR0000068568, TCCC-H-6957, TCCC-GCRC-0654, NCI-V01-1654 |
| Study First Received: | June 6, 2001 |
| Last Updated: | July 23, 2008 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Cancer Institute (NCI):
|
unspecified childhood solid tumor, protocol specific |
Additional relevant MeSH terms:
|
Neoplasms Irinotecan Camptothecin Antineoplastic Agents, Phytogenic Antineoplastic Agents Therapeutic Uses Pharmacologic Actions |
Radiation-Sensitizing Agents Physiological Effects of Drugs Topoisomerase I Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on June 17, 2013