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Carboplatin and Vincristine Plus Radiation Therapy Followed By Adjuvant Chemotherapy in Treating Young Patients With Newly Diagnosed CNS Embryonal 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. Identifier: NCT00003203
Recruitment Status : Completed
First Posted : May 19, 2003
Last Update Posted : August 23, 2013
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as carboplatin and vincristine, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining carboplatin and vincristine with radiation therapy followed by adjuvant chemotherapy may kill more tumor cells.

PURPOSE: Randomized phase II trial to study the effectiveness of combination chemotherapy plus radiation therapy followed adjuvant chemotherapy in treating young patients who have newly diagnosed high-risk CNS embryonal tumors.

Condition or disease Intervention/treatment Phase
Brain Tumors Central Nervous System Tumors Neuroblastoma Biological: filgrastim Drug: carboplatin Drug: cisplatin Drug: cyclophosphamide Drug: vincristine sulfate Procedure: adjuvant therapy Radiation: radiation therapy Phase 2

Detailed Description:


  • Determine the feasible dose and duration of carboplatin combined with craniospinal and local radiotherapy and adjuvant chemotherapy in children with newly diagnosed, high-risk CNS embryonal tumors (Phase I completed as of 11-25-03).
  • Determine the feasibility of administering cyclophosphamide and vincristine with or without cisplatin after concurrent carboplatin, vincristine, and radiotherapy in these patients.
  • Determine the overall and individual toxicity rates of this regimen in these patients.
  • Determine the complete response rate in patients treated with this regimen.
  • Obtain preliminary estimates of event-free survival of patients treated with this regimen.
  • Determine the prognostic significance of enhancing tumor after completion of radiotherapy on event-free survival of these patients.

OUTLINE: This is a pilot, dose-escalation study of carboplatin. (Phase I completed as of 11-25-03.)

Within 31 days of definitive surgery, all patients receive vincristine IV weekly for 6 weeks and carboplatin IV over 15-20 minutes (after completion of vincristine infusion) 5 days a week for 6 weeks. Patients undergo radiotherapy (1-4 hours after carboplatin infusion) 5 days a week for 6 weeks.

Cohorts of 6-12 patients receive escalating doses of carboplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 3 of 12 patients experience dose-limiting toxicity. (Phase I completed as of 11-25-03.)

At 6 weeks after completion of radiotherapy, patients are assigned to arm II for adjuvant/maintenance chemotherapy. (Arm I closed to accrual as of 11-25-03.)

  • Arm I (closed to accrual as of 11-25-03): Patients receive cyclophosphamide IV over 1 hour on days 0 and 1, vincristine IV on days 0 and 7, and filgrastim (G-CSF) IV or subcutaneously (SC) beginning on day 2 and continuing for at least 10 days until blood counts recover.
  • Arm II: Patients receive cyclophosphamide IV over 1 hour on days 1 and 2, vincristine IV on days 0 and 7, cisplatin IV over 6 hours on day 0, and G-CSF IV or SC beginning on day 3 and continuing for at least 10 days until blood counts recover.

In both arms, adjuvant/maintenance chemotherapy repeats every 4 weeks for 6 courses.

Patients are followed every 3 months for 8 months, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 162 patients will be accrued for this study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 168 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Intergroup Pilot Study of Concurrent Carboplatin, Vincristine and Radiotherapy Followed by Adjuvant Chemotherapy in Patients With Newly Diagnosed High-Risk Central Nervous System Embryonal Tumors
Study Start Date : March 1998
Actual Primary Completion Date : October 2007
Actual Study Completion Date : March 2012

Arm Intervention/treatment
Experimental: Newly diagnosed cerebral PNET with histologic verification
Begin therapy within 31 days of surgery. Radiation therapy will be given in standard fractions along with filgrastim. The craniospinal axis will be treated first. Patients will receive carboplatin at 35 mg/m2/day IV over 15-20 minutes Monday through Friday, 1-4 hours prior to radiation for 6 weeks (total of 30 doses). Vincristine sulfate 1.5 mg/m2 IV will be given weekly x 6. Following radiation, patients will receive Maintenance chemotherapy. Patients enrolled prior to Amendment #5 will receive six cycles of cyclophosphamide and vincristine (Regimen A). Patients enrolled after Amendment #5 will receive six cycles of cyclophosphamide, vincristine sulfate and cisplatin (Regimen B).
Biological: filgrastim
Given IV
Other Names:
  • G-CSF
  • Neupogen
  • NSC-614629

Drug: carboplatin
Given IV
Other Names:
  • Paraplatin
  • NSC-241240

Drug: cisplatin
Given IV
Other Names:
  • Platinol-AQ
  • NSC-119875

Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC-26271

Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • NSC-67574

Procedure: adjuvant therapy
Radiation: radiation therapy
1.8 Gy/fx x 20fx=36Gy Craniospinal XRT*
Other Name: radiotherapy

Primary Outcome Measures :
  1. Event Free Survival [ Time Frame: Length of study ]
    Minimum time to disease progression or recurrence, time to death for any reason, or time to occurrence of a second malignant neoplasm (SMN).

Secondary Outcome Measures :
  1. Survival [ Time Frame: Length of study ]
    Time to death from any cause

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   3 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically proven high-risk CNS embryonal tumors, including:

    • Primitive neuroectodermal tumors
    • Atypical teratoid/rhabdoid tumor
    • Medulloblastoma
    • Desmoplastic medulloblastoma
    • Ependymoblastoma
    • Medullomyoblastoma
    • Spongioblastoma
    • Spongioblastoma polare
    • Primitive polar spongioblastoma
    • Neuroepitheliomatous neoplasms
    • Medulloepithelioma
    • Neuroblastoma
    • Pineoblastoma
  • No bone marrow involvement or bone metastases
  • No M4 disease
  • M3 disease must have evidence of tumor on spinal MRI



  • 3 to 21 at diagnosis

Performance status:

  • Not specified

Life expectancy:

  • At least 8 weeks


  • Absolute neutrophil count greater than 1,500/mm^3
  • Platelet count at least 100,000/mm^3 (transfusion independent)
  • Hemoglobin at least 10.0 g/dL (packed red blood cell transfusions allowed)


  • Bilirubin less than 1.5 mg/dL
  • SGOT/SGPT less than 2.5 times normal


  • Creatinine less than 1.5 times upper limit of normal OR
  • Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min


Biologic therapy:

  • Not specified


  • No prior chemotherapy

Endocrine therapy:

  • Not specified


  • No prior radiotherapy


  • Prior definitive surgery allowed

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 identifier (NCT number): NCT00003203

Show Show 38 study locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
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Study Chair: Regina Jakacki, MD University of Pittsburgh
Publications of Results:
Jakacki R, Burger P, Zhou T, et al.: Outcome for metastatic (M+) medulloblastoma (MB) treated with carboplatin during craniospinal radiotherapy (CSRT) followed by cyclophosphamide (CPM) and vincristine (VCR): preliminary results of COG 99701. [Abstract] J Clin Oncol 25 (Suppl 18): A-2017, 2007.

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Responsible Party: Children's Oncology Group Identifier: NCT00003203    
Other Study ID Numbers: A9971
COG-A9971 ( Other Identifier: Children's Oncology Group )
CCG-99701 ( Other Identifier: Children's Cancer Group )
CDR0000066055 ( Other Identifier: Clinical )
First Posted: May 19, 2003    Key Record Dates
Last Update Posted: August 23, 2013
Last Verified: August 2013
Keywords provided by Children's Oncology Group:
untreated childhood supratentorial primitive neuroectodermal tumor
untreated childhood medulloblastoma
localized unresectable neuroblastoma
regional neuroblastoma
stage 4S neuroblastoma
Additional relevant MeSH terms:
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Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents