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Combination Chemotherapy in Treating Children With Progressive Brain Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00002944
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : September 9, 2013
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Description
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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.


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

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 428 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Chemotherapy for Progressive Low Grade Astrocytoma in Children Less Than Ten Years Old
Study Start Date : April 1997
Actual Primary Completion Date : February 2006
Actual Study Completion Date : April 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Brain Tumors

Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]
    Compare the event-free survival as a result of treatment with either CV or TPCV


Secondary Outcome Measures :
  1. Survival [ Time Frame: 5 years ]
    Defined as the time to death from any cause.


Eligibility Criteria
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Ages Eligible for Study:   up to 9 Years   (Child)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00002944


Locations
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Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
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Study Chair: Joann Ater, MD M.D. Anderson Cancer Center
More Information
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Publications of Results:

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Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00002944    
Other Study ID Numbers: A9952
CCG-A9952 ( Other Identifier: Children's Cancer Group )
POG-A9952 ( Other Identifier: Pediatric Oncology Group )
CCG-9952 ( Other Identifier: Clinical Trials.gov )
CDR0000065394 ( Other Identifier: Clinical Trials.gov )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: September 9, 2013
Last Verified: September 2013
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:
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Neoplasms
Brain Neoplasms
Astrocytoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
 Neoplasms, Nerve Tissue
Carboplatin
Vincristine
Thioguanine
Lomustine
Procarbazine
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antineoplastic Agents, Alkylating