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

NCT00138216 | Completed Phase 1 DMC

• 3 other identifiers: ADVL0414COG-ADVL0414CDR0000440069
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 18

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.

Conditions

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

Outcome Measures

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

  length of study

Secondary Outcomes (1)

• To preliminarily define the antitumor activity

  Length of study

Study Arms (1)

Oral Irinotecan, temozolomide and vincristine sulfate

EXPERIMENTAL

see detailed description

Drug: irinotecan hydrochloride; Drug: temozolomide; Drug: vincristine sulfate

Interventions

irinotecan hydrochloride DRUG

Oral Irinotecan, temozolomide and vincristine sulfate

temozolomide DRUG

Oral Irinotecan, temozolomide and vincristine sulfate

vincristine sulfate DRUG

Oral Irinotecan, temozolomide and vincristine sulfate

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (18)

Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

Birmingham, Alabama, 35294, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Stanford Cancer Center

Stanford, California, 94305-5824, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

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

Boston, Massachusetts, 02115, United States

Location

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, 10032, United States

Location

SUNY Upstate Medical University Hospital

Syracuse, New York, 13210, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Oregon Health and Science University Cancer Institute

Portland, Oregon, 97239-3098, United States

Location

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, 18107, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-9786, United States

Location

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

Dallas, Texas, 75390, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Hopital Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (1)

• 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.

  PMID: 20049936 RESULT

MeSH Terms

Conditions

Central Nervous System Neoplasms; Astrocytoma; Familial ependymoma; Medulloblastoma; Optic Nerve Glioma; Oligodendroglioma; Choroid Plexus Neoplasms; Rhabdoid Tumor

Interventions

Irinotecan; Temozolomide; Vincristine

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases; Eye Diseases; Cerebral Ventricle Neoplasms; Brain Neoplasms; Brain Diseases; Central Nervous System Diseases; Neoplasms, Complex and Mixed

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Lars M. Wagner, MD

  Children's Hospital Medical Center, Cincinnati

  STUDY CHAIR

• John P. Perentesis, MD

  Children's Hospital Medical Center, Cincinnati

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2005
• First Posted: August 30, 2005
• Study Start: October 1, 2005
• Primary Completion: June 1, 2009
• Study Completion: January 1, 2011
• Last Updated: October 2, 2023

Record last verified: 2014-02

Locations

US (16); CA (2)