Combination Chemotherapy in Treating Children With Progressive Brain Tumors

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00002944
First received: November 1, 1999
Last updated: September 6, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Brain Tumors
Central Nervous System Tumors
Drug: carboplatin
Drug: lomustine
Drug: procarbazine hydrochloride
Drug: thioguanine
Drug: vincristine sulfate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Chemotherapy for Progressive Low Grade Astrocytoma in Children Less Than Ten Years Old

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Event Free Survival [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Compare the event-free survival as a result of treatment with either CV or TPCV


Secondary Outcome Measures:
  • Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Defined as the time to death from any cause.


Enrollment: 428
Study Start Date: April 1997
Study Completion Date: April 2012
Primary Completion Date: February 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen A (CV Chemotherapy)
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.
Drug: carboplatin
Given IV
Other Names:
  • Paraplatin
  • NSC-241240
Drug: vincristine sulfate
Given PO and IV
Other Names:
  • Oncovin
  • NSC-675574
Experimental: Regimen B (TPCV Chemotherapy)
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.
Drug: lomustine
Given IV
Other Names:
  • CCNU
  • NSC-79037
Drug: procarbazine hydrochloride
Given PO
Other Names:
  • Matulane
  • NSC-77213
Drug: thioguanine
Given PO
Other Names:
  • 6-TG
  • NSC-752
Drug: vincristine sulfate
Given PO and IV
Other Names:
  • Oncovin
  • NSC-675574

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.

  Eligibility

Ages Eligible for Study:   up to 9 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Pathologically confirmed low grade residual astrocytomas or other eligible residual tumors of the brain interpreted as low grade (WHO grades I and II) such as the following:

    • Glial Tumors

      • Astrocytic tumors

        • Low grade astrocytoma (variants: fibrillary, protoplasmic, gemistocytic)
        • Pilocytic astrocytoma
        • Pleomorphic xanthoastrocytomas
        • Subependymal giant cell astrocytoma
        • Infantile desmoplastic astrocytoma
      • Low grade oligodendroglial tumors

        • Low grade oligodendroglioma
      • Low grade mixed gliomas

        • Oligo-astrocytoma
    • Neuronal Tumors

      • Ganglioglioma (excluding tumors with anaplastic astrocytic components)
      • Infantile desmoplastic ganglioglioma
    • Chiasmatic-hypothalamic tumor without histologic confirmation
  • All of the following diagnostic tests (radiological or clinical evidence of progression, surgery, or confirmatory MRI) must be carried out within 6 weeks of enrollment into this study
  • Progressive disease following surgical excision based on clear radiological or clinical evidence of progression, or an incomplete excision (less than 95% or greater than 1.5 cm2) with necessity to begin treatment because of a risk of neurologic impairment with progression
  • Chiasmatic lesions that have contiguous extensions of tumor into other regions of the visual pathways demonstrated on contrast MRI will be eligible for study without histopathological confirmation
  • Patients with neurofibromatosis who have radiographic diagnosis of chiasmatic-hypothalamic tumor are eligible for the study, without requiring a biopsy confirmation of tumor histology, but not unless tumor progression is documented radiographically
  • No intrinsic brain stem tumors of the pons or isolated optic nerve tumors without definitive involvement of the optic chiasm

PATIENT CHARACTERISTICS:

Age:

  • Under 10

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Absolute neutrophil count greater than 1,000/mm^3 (arm II)
  • Platelet count greater than 100,000/mm^3 (arm II)

Hepatic:

  • Not specified

Renal:

  • Creatinine less than 1.5 times upper limit of normal for age OR
  • Creatinine clearance or radioisotope GFR greater than 70 mL/min or equivalent GFR as determined by the institutional normal range

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • No prior chemotherapy for the tumor

Endocrine therapy:

  • Prior corticosteroid therapy allowed

Radiotherapy:

  • No prior radiotherapy for the tumor

Surgery:

  • See Disease characteristics

Other:

  • Prior diuretic therapy allowed
  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: NCT00002944

  Show 204 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Joann Ater, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00002944     History of Changes
Other Study ID Numbers: A9952, CCG-A9952, POG-A9952, CCG-9952, CDR0000065394
Study First Received: November 1, 1999
Last Updated: September 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Oncology Group:
recurrent childhood brain stem glioma
recurrent childhood visual pathway glioma
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
childhood low-grade cerebellar astrocytoma
childhood low-grade cerebral astrocytoma

Additional relevant MeSH terms:
Neoplasms
Brain Neoplasms
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Carboplatin
Vincristine
Procarbazine
Thioguanine
Lomustine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on September 18, 2014