We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Combination Chemotherapy in Treating Children With Progressive Brain Tumors

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00002944
First Posted: January 27, 2003
Last Update Posted: September 9, 2013
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.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
November 1, 1999
January 27, 2003
September 9, 2013
April 1997
February 2006   (Final data collection date for primary outcome measure)
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
Not Provided
Complete list of historical versions of study NCT00002944 on ClinicalTrials.gov Archive Site
Survival [ Time Frame: 5 years ]
Defined as the time to death from any cause.
Not Provided
Not Provided
Not Provided
 
Combination Chemotherapy in Treating Children With Progressive Brain Tumors
Chemotherapy for Progressive Low Grade Astrocytoma in Children Less Than Ten Years Old

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.

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Brain Tumors
  • Central Nervous System Tumors
  • Drug: carboplatin
    Given IV
    Other Names:
    • Paraplatin
    • NSC-241240
  • 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
  • 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.
    Interventions:
    • Drug: carboplatin
    • Drug: vincristine sulfate
  • 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.
    Interventions:
    • Drug: lomustine
    • Drug: procarbazine hydrochloride
    • Drug: thioguanine
    • Drug: vincristine sulfate
Ater JL, Zhou T, Holmes E, Mazewski CM, Booth TN, Freyer DR, Lazarus KH, Packer RJ, Prados M, Sposto R, Vezina G, Wisoff JH, Pollack IF. Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: a report from the Children's Oncology Group. J Clin Oncol. 2012 Jul 20;30(21):2641-7. doi: 10.1200/JCO.2011.36.6054. Epub 2012 Jun 4.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
428
April 2012
February 2006   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
up to 9 Years   (Child)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Canada,   Netherlands,   New Zealand,   Switzerland,   United States
 
 
NCT00002944
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 )
Yes
Not Provided
Not Provided
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Study Chair: Joann Ater, MD M.D. Anderson Cancer Center
Children's Oncology Group
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP