Combination Chemotherapy in Treating Children With Progressive Brain Tumors

Phase 3

Completed

• Conditions: Brain Tumors; Central Nervous System Tumors
• Interventions: Drug: carboplatin; Drug: lomustine; Drug: vincristine sulfate; Drug: procarbazine hydrochloride; Drug: thioguanine

• Registration Number: NCT00002944
• Lead Sponsor: Children's Oncology Group

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: This randomized phase III trial is studying two different combination chemotherapy regimens and comparing how well they work in treating children with low-grade astrocytomas or other residual tumors of the brain.

Detailed Description

OBJECTIVES:

* Compare the event free survival as a result of treatment with carboplatin and vincristine versus thioguanine, procarbazine, lomustine, and vincristine in children with progressive brain tumors.

* Estimate tumor response rates to each regimen of chemotherapy in these patients.

* Determine toxic effects and quality of life of children treated with each regimen of chemotherapy.

* Investigate biological and clinical factors which may predict tumor response and early progression (tumor size, location, pathologic subtype, cytogenetics, and proliferative index by MIB-1 (Ki67)) in these patients.

* Investigate factors contributing to neuropsychological and endocrine status of children with brain tumors treated without irradiation.

OUTLINE: This is a randomized study. Patients are stratified according to site of disease, status at entry, and pathology. Patients are randomized to one of two treatment arms. Patients with neurofibromatosis are nonrandomly assigned to arm II.

* Arm I: Patients receive induction with carboplatin and vincristine for 10 weeks followed by 2 weeks of rest. Induction is followed by 8 courses of maintenance beginning on day 84 of induction or upon hematopoietic recovery. Each course consists of 4 weekly doses of carboplatin and 3 weekly doses of vincristine (given concurrently with the first 3 weeks of carboplatin), followed by 2 weeks of rest.

* Arm II: Patients receive oral thioguanine, procarbazine, and lomustine on days 0-4, followed by vincristine IV on days 14 and 28. Treatment continues every 6 weeks for a maximum of 8 courses.

PROJECTED ACCRUAL: A total of 280-340 patients will be accrued over 4 years.

Study Timeline

• Study Start: 1997-04
• Study First Submitted: 1999-11-01
• Study First Submitted QC: 2003-01-26
• Study First Posted: 2003-01-27
• Primary Completion: 2006-02
• Study Completion: 2012-04
• Status Verified: 2013-09
• Last Update Submitted: 2013-09-06
• Last Update Posted: 2013-09-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 428

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Regimen A (CV Chemotherapy)	vincristine sulfate	Induction will consist of 10 weeks of therapy (carboplatin, vincristine sulfate),followed by 2 weeks without chemotherapy. Induction should only be interrupted in the event of grade 3 neurotoxicity, grade 2 renal toxicity, grade 4 hematologic toxicity, or tumor progression. Maintenance-Four Courses (2 cycles/course) commences on Day 84 (week 12) of Induction or when peripheral counts recover with ANC \>1,000/$L and platelet count \>100,000/$L. Each cycle will consist of 4 weekly doses of carboplatin, three weekly doses of vincristine sulfate (given concomitantly with the first 3 weeks of carboplatin), followed by two weeks of rest for a total of 6 weeks. Maintenance will continue for a total of 8 cycles.
Regimen B (TPCV Chemotherapy)	procarbazine hydrochloride	Each cycle of chemotherapy consists of 4 days of oral chemotherapy (Thioguanine, procarbazine hydrochloride, Lomustine and Vincristine sulfate beginning Day 0, followed by vincristine sulfate IV on Days 14 and 28. The cycle is repeated every 6 weeks (42 days). A total of 8 cycles will be given.
Regimen B (TPCV Chemotherapy)	vincristine sulfate	Each cycle of chemotherapy consists of 4 days of oral chemotherapy (Thioguanine, procarbazine hydrochloride, Lomustine and Vincristine sulfate beginning Day 0, followed by vincristine sulfate IV on Days 14 and 28. The cycle is repeated every 6 weeks (42 days). A total of 8 cycles will be given.
Regimen A (CV Chemotherapy)	carboplatin	Induction will consist of 10 weeks of therapy (carboplatin, vincristine sulfate),followed by 2 weeks without chemotherapy. Induction should only be interrupted in the event of grade 3 neurotoxicity, grade 2 renal toxicity, grade 4 hematologic toxicity, or tumor progression. Maintenance-Four Courses (2 cycles/course) commences on Day 84 (week 12) of Induction or when peripheral counts recover with ANC \>1,000/$L and platelet count \>100,000/$L. Each cycle will consist of 4 weekly doses of carboplatin, three weekly doses of vincristine sulfate (given concomitantly with the first 3 weeks of carboplatin), followed by two weeks of rest for a total of 6 weeks. Maintenance will continue for a total of 8 cycles.
Regimen B (TPCV Chemotherapy)	lomustine	Each cycle of chemotherapy consists of 4 days of oral chemotherapy (Thioguanine, procarbazine hydrochloride, Lomustine and Vincristine sulfate beginning Day 0, followed by vincristine sulfate IV on Days 14 and 28. The cycle is repeated every 6 weeks (42 days). A total of 8 cycles will be given.
Regimen B (TPCV Chemotherapy)	thioguanine	Each cycle of chemotherapy consists of 4 days of oral chemotherapy (Thioguanine, procarbazine hydrochloride, Lomustine and Vincristine sulfate beginning Day 0, followed by vincristine sulfate IV on Days 14 and 28. The cycle is repeated every 6 weeks (42 days). A total of 8 cycles will be given.

Primary Outcome Measures

Name	Time	Method
Event Free Survival	Time from study entry until disease progression, death without progression of disease, occurrence of a second malignant neoplasm or last follow-up, whichever comes first, assessed up to 5 years	Compare the event-free survival as a result of treatment with either CV or TPCV

Secondary Outcome Measures

Name	Time	Method
Survival	5 years	Defined as the time to death from any cause.

Trial Locations

Locations (204)

University of South Alabama Mitchell Cancer Institute; 🇺🇸 Mobile, Alabama, United States

Phoenix Children's Hospital; 🇺🇸 Phoenix, Arizona, United States

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

Southern California Permanente Medical Group; 🇺🇸 Downey, California, United States

City of Hope Comprehensive Cancer Center; 🇺🇸 Duarte, California, United States

Loma Linda University Cancer Institute at Loma Linda University Medical Center; 🇺🇸 Loma Linda, California, United States

Jonathan Jaques Children's Cancer Center at Miller Children's Hospital; 🇺🇸 Long Beach, California, United States

Childrens Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Jonsson Comprehensive Cancer Center at UCLA; 🇺🇸 Los Angeles, California, United States

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