Carboplatin and Vincristine Plus Radiation Therapy Followed By Adjuvant Chemotherapy in Treating Young Patients With Newly Diagnosed CNS Embryonal Tumors

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00003203
First received: November 1, 1999
Last updated: August 22, 2013
Last verified: August 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Event Free Survival [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]
    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:
  • Survival [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]
    Time to death from any cause


Enrollment: 168
Study Start Date: March 1998
Study Completion Date: March 2012
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

OBJECTIVES:

  • 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.

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age:

  • 3 to 21 at diagnosis

Performance status:

  • Not specified

Life expectancy:

  • At least 8 weeks

Hematopoietic:

  • 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)

Hepatic:

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

Renal:

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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • No prior chemotherapy

Endocrine therapy:

  • Not specified

Radiotherapy:

  • No prior radiotherapy

Surgery:

  • Prior definitive surgery 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: NCT00003203

  Show 38 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Regina Jakacki, MD Children's Hospital of Pittsburgh of UPMC
  More Information

Additional Information:
Publications:
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.

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00003203     History of Changes
Other Study ID Numbers: A9971, COG-A9971, CCG-99701, CDR0000066055
Study First Received: November 1, 1999
Last Updated: August 22, 2013
Health Authority: United States: Food and Drug Administration

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:
Central Nervous System Neoplasms
Neoplasms
Nervous System Neoplasms
Neuroblastoma
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Nervous System Diseases
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Carboplatin
Cisplatin
Cyclophosphamide
Vincristine
Alkylating Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 20, 2014