Irinotecan in Treating Children With Refractory or Progressive Solid Tumors

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00016861
First received: June 6, 2001
Last updated: June 25, 2013
Last verified: November 2004
  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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: September 1998
Study Completion Date: January 2005
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.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00016861

Locations
United States, Texas
Texas Children's Cancer Center
Houston, Texas, United States, 77030-2399
Sponsors and Collaborators
Texas Children's Cancer Center
Investigators
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: TCCC-H-6957, CDR0000068568, TCCC-GCRC-0654, NCI-V01-1654
Study First Received: June 6, 2001
Last Updated: June 25, 2013
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 July 20, 2014