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Brain and Central Nervous System TumorsPhase 1NCT00138216

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

A Phase 1 study testing irinotecan hydrochloride, temozolomide and vincristine sulfate in people with Brain and Central Nervous System Tumors and Unspecified Childhood Solid Tumor, Protocol Specific, run by Children's Oncology Group at 18 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?
Ages 1 year to 21 years
What is being tested?
irinotecan hydrochloride, temozolomide and vincristine sulfate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
18 sitesin 2 countries
Study dates
Oct 2005to Jan 2011
Phase
Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

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

Trial locations and contacts

18 sites in 2 countries.

18 sites in 2 countries

United States16 sites
  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18107

  • Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

    Birmingham, Alabama, 35294

  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Children's Memorial Hospital - Chicago

    Chicago, Illinois, 60614

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229-3039

  • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

    Dallas, Texas, 75390

  • Indiana University Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202-5289

  • Masonic Cancer Center at University of Minnesota

    Minneapolis, Minnesota, 55455

  • Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

    New York, New York, 10032

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104-9786

  • Oregon Health and Science University Cancer Institute

    Portland, Oregon, 97239-3098

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • Children's Hospital and Regional Medical Center - Seattle

    Seattle, Washington, 98105

  • Stanford Cancer Center

    Stanford, California, 94305-5824

  • SUNY Upstate Medical University Hospital

    Syracuse, New York, 13210

Other trials in United States

Canada2 sites
  • Hopital Sainte Justine

    Montreal, Quebec, H3T 1C5

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

Other trials in Canada

About this study

Official title: A Phase I Study of Temozolomide, Oral Irinotecan, and Vincristine for Children With Refractory Solid Tumors

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.

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
Medical subject headings
Central Nervous System Neoplasms, Astrocytoma, Familial ependymoma, Medulloblastoma, Optic Nerve Glioma, Oligodendroglioma, Choroid Plexus Neoplasms, Rhabdoid Tumor

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00138216
Study groupRoleWhat they receive
Oral Irinotecan, temozolomide and vincristine sulfateExperimentalsee detailed description
Receives: Drug: irinotecan hydrochloride; Drug: temozolomide; Drug: vincristine sulfate

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: length of study

Secondary outcomes (1)
  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.

    Measured: Length of study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Aug 2005 (estimated)
  2. Study startOct 2005
  3. Primary completionJun 2009
  4. Study completionJan 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00138216
Sponsor's protocol ID
ADVL0414
Other IDs
COG-ADVL0414, CDR0000440069
Status last verified
Feb 2014
First submitted
29 Aug 2005
Last updated
2 Oct 2023
Results posted
No
Data monitoring committee
Yes

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

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