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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00138216
First received: August 29, 2005
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Temozolomide, Oral Irinotecan, and Vincristine for Children With Refractory Solid Tumors

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Determine maximum tolerated dose (MTD) of oral irinotecan [ Time Frame: length of study ] [ Designated as safety issue: Yes ]
    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:
  • To preliminarily define the antitumor activity [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]
    To preliminarily define the antitumor activity of this drug combination within the confines of a Phase 1 study.


Enrollment: 42
Study Start Date: October 2005
Study Completion Date: January 2011
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oral Irinotecan, temozolomide and vincristine sulfate
see detailed description
Drug: irinotecan hydrochloride Drug: temozolomide Drug: vincristine sulfate

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.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00138216

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

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00138216     History of Changes
Other Study ID Numbers: ADVL0414, COG-ADVL0414, CDR0000440069
Study First Received: August 29, 2005
Last Updated: February 18, 2014
Health Authority: United States: Federal Government

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:
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms
Neoplasms by Site
Nervous System Diseases
Vincristine
Irinotecan
Camptothecin
Temozolomide
Dacarbazine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014