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Temozolomide, Vincristine, and Irinotecan in Treating Young Patients With Refractory Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00138216
Recruitment Status : Completed
First Posted : August 30, 2005
Last Update Posted : February 20, 2014
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as temozolomide, vincristine, and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of irinotecan when given together with temozolomide and vincristine in treating young patients with refractory solid tumors.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Unspecified Childhood Solid Tumor, Protocol Specific Drug: irinotecan hydrochloride Drug: temozolomide Drug: vincristine sulfate Phase 1

Detailed Description:



  • Determine the maximum tolerated dose and recommended phase II dose of irinotecan when administered with temozolomide and vincristine in young patients with refractory solid tumors, including brain tumors.
  • Determine the toxic effects of this regimen in these patients.
  • Compare the toxic effects of this regimen in patients with low- vs high-risk UGT1A1 genotypes.
  • Determine the pharmacokinetics of irinotecan in these patients.


  • Determine, preliminarily, the antitumor activity of this regimen in these patients.
  • Correlate UGT1A1, UGT1A7, UGT1A9, and BCRP genotypes with the pharmacokinetics and pharmacodynamics of irinotecan and its metabolites in these patients.

OUTLINE: This is a multicenter, dose-escalation study of irinotecan. Patients are stratified according to UGT1A1 genotype (high-risk [7/7 or 6/7 genotype AND bilirubin ≥ 0.6 mg/dL] vs low-risk [absence of high-risk criteria]) if a high-risk patient experiences a dose-limiting toxicity (DLT).

Patients receive oral temozolomide on days 1-5 and oral irinotecan on days 1-5 and 8-12. Patients also receive vincristine IV over 1 minute on days 1 and 8. Treatment repeats every 21 days for up to 17 courses 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) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience DLT.

After completion of study treatment, patients are followed for 1 month and then annually thereafter.

PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study within 18 months.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Temozolomide, Oral Irinotecan, and Vincristine for Children With Refractory Solid Tumors
Study Start Date : October 2005
Actual Primary Completion Date : June 2009
Actual Study Completion Date : January 2011

Arm Intervention/treatment
Experimental: Oral Irinotecan, temozolomide and vincristine sulfate
see detailed description
Drug: irinotecan hydrochloride
Drug: temozolomide
Drug: vincristine sulfate

Primary Outcome Measures :
  1. Determine maximum tolerated dose (MTD) of oral irinotecan [ Time Frame: length of study ]
    To estimate the maximum tolerated dose (MTD) of oral irinotecan administered on two different schedules together with fixed-dose temozolomide and vincristine in children with refractory solid tumors or brain tumors

Secondary Outcome Measures :
  1. To preliminarily define the antitumor activity [ Time Frame: Length of study ]
    To preliminarily define the antitumor activity of this drug combination within the confines of a Phase 1 study.

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed* malignant solid tumor, including brain tumor, at original diagnosis or relapse

    • Refractory disease NOTE: *Histologic confirmation not required for intrinsic brain stem tumors
  • Measurable or evaluable disease
  • No known curative therapy OR therapy proven to prolong survival with an acceptable quality of life exists
  • No known bone marrow metastases



  • 1 to 21

Performance status

  • Lansky 50-100% (for patients ≤ 10 years of age)
  • Karnofsky 50-100% (for patients > 10 years of age)

Life expectancy

  • Not specified


  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3 (transfusion independent)
  • Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)


  • ALT ≤ 110 U/L (upper limit of normal [ULN] for ALT is 45 U/L)
  • Bilirubin ≤ 1.5 times ULN
  • Albumin ≥ 2 g/dL


  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR
  • Creatinine based on age as follows:

    • No greater than 0.8 mg/dL (for patients ≤ 5 years of age)
    • No greater than 1.0 mg/dL (for patients 6 to 10 years of age)
    • No greater than 1.2 mg/dL (for patients 11 to 15 years of age)
    • No greater than 1.5 mg/dL (for patients > 15 years of age)


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Neurologic deficits in patients with CNS tumors must be stable for ≥ 1 week prior to study entry
  • No uncontrolled infection
  • No documented allergy to cephalosporins or dacarbazine


Biologic therapy

  • Recovered from prior immunotherapy
  • At least 3 months since prior stem cell transplantation or rescue without total-body irradiation

    • No evidence of active graft-versus-host disease
  • At least 7 days since prior antineoplastic biologic agents
  • At least 7 days since prior hematopoietic growth factors
  • No concurrent biologic therapy or immunotherapy
  • No concurrent prophylactic filgrastim (G-CSF) during the first course of study treatment


  • Recovered from prior chemotherapy
  • Prior temozolomide, vincristine, irinotecan, or topotecan allowed

    • No prior coadministration of temozolomide and irinotecan
    • No disease progression during treatment with either irinotecan or temozolomide
  • More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)
  • No other concurrent chemotherapy

Endocrine therapy

  • Patients with CNS tumors must be on a stable or decreasing dose of dexamethasone for ≥ 7 days prior to study entry


  • Recovered from prior radiotherapy
  • At least 6 months since prior total-body irradiation, craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis
  • At least 6 weeks since other prior substantial bone marrow radiotherapy
  • At least 2 weeks since prior local palliative radiotherapy (small port)
  • No concurrent radiotherapy


  • Not specified


  • No other concurrent investigational drugs
  • No other concurrent anticancer therapy
  • No concurrent enzyme-inducing anticonvulsants, including any of the following:

    • Phenobarbital
    • Phenytoin
    • Carbamazepine
    • Oxcarbazepine
  • No concurrent administration of any of the following:

    • Rifampin
    • Voriconazole
    • Itraconazole
    • Ketoconazole
    • Aprepitant
    • Hypericum perforatum (St. John's wort)
  • No concurrent treatment for clostridium difficile infection

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00138216

Show Show 18 study locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
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Study Chair: Lars M. Wagner, MD Children's Hospital Medical Center, Cincinnati
Study Chair: John P. Perentesis, MD Children's Hospital Medical Center, Cincinnati
Publications of Results:
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Responsible Party: Children's Oncology Group Identifier: NCT00138216    
Other Study ID Numbers: ADVL0414
COG-ADVL0414 ( Other Identifier: Children's Oncology Group )
CDR0000440069 ( Other Identifier: )
First Posted: August 30, 2005    Key Record Dates
Last Update Posted: February 20, 2014
Last Verified: February 2014
Keywords provided by Children's Oncology Group:
unspecified childhood solid tumor, protocol specific
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
recurrent childhood brain stem glioma
recurrent childhood brain tumor
recurrent childhood ependymoma
recurrent childhood medulloblastoma
recurrent childhood supratentorial primitive neuroectodermal tumor
recurrent childhood visual pathway and hypothalamic glioma
childhood oligodendroglioma
childhood craniopharyngioma
childhood choroid plexus tumor
childhood infratentorial ependymoma
childhood supratentorial ependymoma
childhood high-grade cerebral astrocytoma
childhood low-grade cerebral astrocytoma
childhood central nervous system germ cell tumor
childhood grade I meningioma
childhood grade II meningioma
childhood grade III meningioma
recurrent childhood subependymal giant cell astrocytoma
childhood atypical teratoid/rhabdoid tumor
Additional relevant MeSH terms:
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Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Alkylating
Alkylating Agents