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CompletedNCT00138216Updated Oct 2, 2023

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

A Phase 1 interventional study of irinotecan hydrochloride and temozolomide in Brain and Central Nervous System Tumors and Unspecified Childhood Solid Tumor, Protocol Specific, sponsored by Children's Oncology Group. Completed at 18 sites in 2 countries. Open to participants aged 1 Year to 21 Years. Per ClinicalTrials.gov, last updated 2023-10-02.

Sponsored by Children's Oncology Group · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
42
Allocation
Not applicable
Ages
1 Year to 21 Years
Sex
All
01

Study 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.

Read the detailed description

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

02

Conditions studied

  • Brain and Central Nervous System Tumors
  • Unspecified Childhood Solid Tumor, Protocol Specific

Keywords

  • 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
03

In context

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.

This study's enrollment of 42 is below the median of 50 across 7,253 interventional studies indexed under Neoplasms.

Browse Neoplasms studies →

Lead sponsor

Children's Oncology Group is the lead sponsor of 436 studies on the registry; 34 are open to participants now.

Of its 12 completed or terminated interventional studies of FDA-regulated products, 11 (92%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
1 Year to 21 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age

  • 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

Hematopoietic

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

Hepatic

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

Renal

  • 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)

Other

  • 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

PRIOR CONCURRENT THERAPY:

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

Chemotherapy

  • 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

Radiotherapy

  • 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

Surgery

  • Not specified

Other

  • 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
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
42 participants (actual)

Study arms

  • Experimental
    Oral Irinotecan, temozolomide and vincristine sulfate

    see detailed description

    Drug: irinotecan hydrochloride · Drug: temozolomide · Drug: vincristine sulfate

Interventions

  • Drugirinotecan hydrochloride
  • Drugtemozolomide
  • Drugvincristine sulfate
06

What researchers measure

Primary outcomes

  1. Determine maximum tolerated dose (MTD) of oral irinotecan

    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

    Time frame: length of study

Secondary outcomes

  1. To preliminarily define the antitumor activity

    To preliminarily define the antitumor activity of this drug combination within the confines of a Phase 1 study.

    Time frame: Length of study

07

Study locations

18 sites
  • Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
    Birmingham, Alabama 35294, United States
  • Children's Hospital of Orange County
    Orange, California 92868, United States
  • Stanford Cancer Center
    Stanford, California 94305-5824, United States
  • Children's Memorial Hospital - Chicago
    Chicago, Illinois 60614, United States
  • Indiana University Melvin and Bren Simon Cancer Center
    Indianapolis, Indiana 46202-5289, United States
  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    Boston, Massachusetts 02115, United States
  • Masonic Cancer Center at University of Minnesota
    Minneapolis, Minnesota 55455, United States
  • Mayo Clinic Cancer Center
    Rochester, Minnesota 55905, United States
  • Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
    New York, New York 10032, United States
  • SUNY Upstate Medical University Hospital
    Syracuse, New York 13210, United States
  • Cincinnati Children's Hospital Medical Center
    Cincinnati, Ohio 45229-3039, United States
  • Oregon Health and Science University Cancer Institute
    Portland, Oregon 97239-3098, United States
  • Lehigh Valley Hospital - Muhlenberg
    Bethlehem, Pennsylvania 18107, United States
  • Children's Hospital of Philadelphia
    Philadelphia, Pennsylvania 19104-9786, United States
  • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
    Dallas, Texas 75390, United States
  • Children's Hospital and Regional Medical Center - Seattle
    Seattle, Washington 98105, United States
  • Hospital for Sick Children
    Toronto, Ontario M5G 1X8, Canada
  • Hopital Sainte Justine
    Montreal, Quebec H3T 1C5, Canada
08

References and documents

Publications

  • Wagner LM, Perentesis JP, Reid JM, Ames MM, Safgren SL, Nelson MD Jr, Ingle AM, Blaney SM, Adamson PC. Phase I trial of two schedules of vincristine, oral irinotecan, and temozolomide (VOIT) for children with relapsed or refractory solid tumors: a Children's Oncology Group phase I consortium study. Pediatr Blood Cancer. 2010 Apr;54(4):538-45. doi: 10.1002/pbc.22407. PubMed 20049936 ↗
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 2, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00138216
Lead sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Aug 30, 2005
Start date
Oct 2005
Primary completion
Jun 2009
Completion
Jan 2011
Last update
Oct 2, 2023

Study contacts

Lars M. Wagner, MD
study chair · Children's Hospital Medical Center, Cincinnati
John P. Perentesis, MD
study chair · Children's Hospital Medical Center, Cincinnati

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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