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

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003203

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 and Central Nervous System Tumors Neuroblastoma	Biological: filgrastim Drug: carboplatin Drug: cisplatin Drug: cyclophosphamide Drug: vincristine sulfate Procedure: adjuvant therapy Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	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:

MedlinePlus related topics: Cancer Neuroblastoma

Drug Information available for: Cyclophosphamide Vincristine Cisplatin Carboplatin Filgrastim Vincristine sulfate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	162
Study Start Date:	March 1998
Primary Completion Date:	October 2007 (Final data collection date for primary outcome measure)

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003203

Show 38 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Regina Jakacki, MD

Children's Hospital of Pittsburgh

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

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.

Study ID Numbers:	CDR0000066055, COG-A9971, CCG-99701
Study First Received:	November 1, 1999
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00003203 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

untreated childhood supratentorial primitive neuroectodermal tumor
untreated childhood medulloblastoma
localized unresectable neuroblastoma
regional neuroblastoma
stage 4S neuroblastoma

Additional relevant MeSH terms:

Neuroectodermal Tumors, Primitive
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Central Nervous System Neoplasms
Cyclophosphamide
Neuroblastoma
Neoplasms by Site
Cisplatin
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Alkylating Agents
Nervous System Neoplasms

Neoplasms by Histologic Type
Mitosis Modulators
Nervous System Diseases
Adjuvants, Immunologic
Vincristine
Antimitotic Agents
Carboplatin
Immunosuppressive Agents
Pharmacologic Actions
Neuroectodermal Tumors
Neoplasms
Radiation-Sensitizing Agents
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on November 27, 2009