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

NCT ID: NCT00003203

Last Updated: 2013-08-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

168 participants

Study Classification

INTERVENTIONAL

Study Start Date

1998-03-31

Study Completion Date

2012-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Brain Tumors Central Nervous System Tumors Neuroblastoma

Keywords

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

Given IV

carboplatin

Intervention Type DRUG

Given IV

cisplatin

Intervention Type DRUG

Given IV

cyclophosphamide

Intervention Type DRUG

Given IV

vincristine sulfate

Intervention Type DRUG

Given IV

adjuvant therapy

Intervention Type PROCEDURE

radiation therapy

Intervention Type RADIATION

1.8 Gy/fx x 20fx=36Gy Craniospinal XRT\*

Interventions

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filgrastim

Given IV

Intervention Type BIOLOGICAL

carboplatin

Given IV

Intervention Type DRUG

cisplatin

Given IV

Intervention Type DRUG

cyclophosphamide

Given IV

Intervention Type DRUG

vincristine sulfate

Given IV

Intervention Type DRUG

adjuvant therapy

Intervention Type PROCEDURE

radiation therapy

1.8 Gy/fx x 20fx=36Gy Craniospinal XRT\*

Intervention Type RADIATION

Other Intervention Names

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G-CSF Neupogen NSC-614629 Paraplatin NSC-241240 Platinol-AQ NSC-119875 Cytoxan NSC-26271 Oncovin NSC-67574 radiotherapy

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

3 Years

Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Regina Jakacki, MD

Role: STUDY_CHAIR

University of Pittsburgh

Locations

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Long Beach Memorial Medical Center

Long Beach, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

Site Status

Children's Hospital of Denver

Denver, Colorado, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

Indiana University Cancer Center

Indianapolis, Indiana, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

CCOP - Kalamazoo

Kalamazoo, Michigan, United States

Site Status

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

St. Joseph's Hospital and Medical Center

Paterson, New Jersey, United States

Site Status

NYU School of Medicine's Kaplan Comprehensive Cancer Center

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, United States

Site Status

CCOP - Merit Care Hospital

Fargo, North Dakota, United States

Site Status

Children's Hospital Medical Center - Cincinnati

Cincinnati, Ohio, United States

Site Status

Ireland Cancer Center

Cleveland, Ohio, United States

Site Status

Children's Hospital of Columbus

Columbus, Ohio, United States

Site Status

Doernbecher Children's Hospital

Portland, Oregon, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt Cancer Center

Nashville, Tennessee, United States

Site Status

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Site Status

IWK Grace Health Centre

Halifax, Nova Scotia, Canada

Site Status

Countries

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United States Australia Canada

References

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Jakacki RI, Burger PC, Zhou T, Holmes EJ, Kocak M, Onar A, Goldwein J, Mehta M, Packer RJ, Tarbell N, Fitz C, Vezina G, Hilden J, Pollack IF. Outcome of children with metastatic medulloblastoma treated with carboplatin during craniospinal radiotherapy: a Children's Oncology Group Phase I/II study. J Clin Oncol. 2012 Jul 20;30(21):2648-53. doi: 10.1200/JCO.2011.40.2792. Epub 2012 Jun 4.

Reference Type RESULT
PMID: 22665539 (View on PubMed)

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.

Reference Type RESULT

Other Identifiers

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COG-A9971

Identifier Type: OTHER

Identifier Source: secondary_id

CCG-99701

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000066055

Identifier Type: OTHER

Identifier Source: secondary_id

A9971

Identifier Type: -

Identifier Source: org_study_id