Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Newly Diagnosed Brain Stem Glioma

NCT ID: NCT00003625

Last Updated: 2014-07-28

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

PHASE1

Total Enrollment

7 participants

Study Classification

INTERVENTIONAL

Study Start Date

1998-12-31

Study Completion Date

2006-04-30

Brief Summary

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RATIONALE: Drugs used in chemotherapy use 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 more than one chemotherapy drug with radiation therapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus radiation therapy in treating patients with newly diagnosed brain stem glioma.

Detailed Description

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OBJECTIVES: I. Determine the maximum tolerated dose and dose limiting toxicity of vincristine given as an IV push dose in combination with continuous infusion cyclosporine and oral etoposide concurrent with and prior to radiotherapy in children with newly diagnosed primary intrinsic brain stem glioma. II. Determine the incidence and severity of other toxicities of vincristine in this regimen in these patients. III. Determine a safe and tolerable dose of vincristine under these conditions to be used in phase II studies. IV. Seek preliminary evidence of antitumor activity in this setting in these patients.

OUTLINE: This is dose escalation study of vincristine. Patients receive radiotherapy daily for 6 weeks with concurrent induction chemotherapy. Induction chemotherapy consists of vincristine IV push weekly for 6 weeks, oral etoposide daily on days 1-21 and 29-49 and cyclosporine IV over 2 hours prior to vincristine followed by a continuous 36 hour infusion. Cohorts of 3-6 patients receive escalating doses of vincristine. If dose limiting toxicity (DLT) occurs in 2 or more of 3-6 patients, the maximum tolerated dose (MTD) has been exceeded and the preceding dose is declared the MTD. Maintenance therapy consists of 6 monthly courses of cyclosporine IV over 36 hours beginning on day 1, vincristine IV push on day 1, and oral etoposide daily for days 1-21. Patients are followed every 6 months for 4 years and then annually thereafter.

PROJECTED ACCRUAL: At least 6 patients will be accrued into this study at a rate of 12 patients per year.

Conditions

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Brain Tumors Central Nervous System Tumors

Study Design

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Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Stratum 1

Concomitant irradiation and vincristine sulfate in esc dose beginning with 0.8 mg/m2, etoposide and Cyclosporine A given over 6 weeks, then monthly maint courses over 6 mths, with no clinical and radiologic progression. Stable disease indicates continuation of therapy. Clinical deterioration within 4 months of completion of radiation therapy must be confirmed to be PD by imaging. Clinical progression even in the absence of imaging changes will be accepted as reflecting disease progression. Steroids dexamethasone (Decadron) given as clinically indicated and tapered as tolerated. Steroids may decrease capillary permeability to chemotherapeutic agents and antagonise the effect of cyclosporin A. Also contributes to the syndrome of seizures and white matter changes seen with cyclosporine in the post BMT period. If steroid use is required, the recommended schedule of Decadron dosing during the 6 week induction course is 8 mg/m2 divided q 6-8 hours.

Group Type EXPERIMENTAL

cyclosporine

Intervention Type DRUG

etoposide

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

radiation therapy

Intervention Type RADIATION

Interventions

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cyclosporine

Intervention Type DRUG

etoposide

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

radiation therapy

Intervention Type RADIATION

Other Intervention Names

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CSA NSC # 290193 VP-16 VePesid NSC # 141540 VCR Oncovin NSC # 067574

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS: Newly diagnosed diffuse intrinsic brain stem glioma by MRI Biopsy is neither necessary nor encouraged A least two-thirds of the tumor is in the pons Origin of the tumor is clearly in the pons Must be registered within 28 days of diagnosis Clinical history less than 6 months duration (cranial nerve deficit, long tract signs, or ataxia) No diffuse leptomeningeal disease

PATIENT CHARACTERISTICS: Age: 3 to 21 Performance status: Karnofsky or Lansky 50-100% Life expectancy: At least 6 weeks Hematopoietic: Absolute neutrophil count at least 1,000/mm3 Platelet count at least 75,000/mm3 Hepatic: SGPT less than 2 times normal Renal: Creatinine normal for age OR Creatinine clearance greater than 70 mL/min

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy Chemotherapy: No prior chemotherapy No other concurrent chemotherapy Endocrine therapy: Prior steroids at stable or decreasing doses allowed Radiotherapy: No prior radiotherapy Surgery: Not specified Other: No other concurrent investigational agents
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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Mark L. Greenberg, MD

Role: STUDY_CHAIR

The Hospital for Sick Children

Locations

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University of Alabama Comprehensive Cancer Center

Birmingham, Alabama, United States

Site Status

Arizona Cancer Center

Tucson, Arizona, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

University of California San Diego Cancer Center

La Jolla, California, United States

Site Status

Lucile Packard Children's Hospital at Stanford

Palo Alto, California, United States

Site Status

Sutter Cancer Center

Sacramento, California, United States

Site Status

Kaiser Permanente-Southern California Permanente Medical Group

San Diego, California, United States

Site Status

Naval Medical Center - San Diego

San Diego, California, United States

Site Status

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, United States

Site Status

Nemours Children's Clinic

Jacksonville, Florida, United States

Site Status

Sylvester Cancer Center, University of Miami

Miami, Florida, United States

Site Status

Baptist Hospital of Miami

Miami, Florida, United States

Site Status

Walt Disney Memorial Cancer Institute

Orlando, Florida, United States

Site Status

St. Mary's Hospital

West Palm Beach, Florida, United States

Site Status

Emory University Hospital - Atlanta

Atlanta, Georgia, United States

Site Status

Tripler Army Medical Center

Honolulu, Hawaii, United States

Site Status

Rush-Presbyterian-St. Luke's Medical Center

Chicago, Illinois, United States

Site Status

Children's Memorial Hospital, Chicago

Chicago, Illinois, United States

Site Status

Christ Hospital

Oak Lawn, Illinois, United States

Site Status

Saint Jude Midwest Affiliate

Peoria, Illinois, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Via Christi Regional Medical Center-Saint Francis Campus

Wichita, Kansas, United States

Site Status

Tulane University School of Medicine

New Orleans, Louisiana, United States

Site Status

Eastern Maine Medical Center

Bangor, Maine, United States

Site Status

Maine Children's Cancer Program

Portland, Maine, United States

Site Status

Johns Hopkins Oncology Center

Baltimore, Maryland, United States

Site Status

Floating Hospital for Children

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status

St. John's Hospital and Medical Center

Detroit, Michigan, United States

Site Status

Hurley Medical Center

Flint, Michigan, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Keesler Medical Center - Keesler AFB

Keesler Air Force Base, Mississippi, United States

Site Status

University of Missouri-Columbia Hospital and Clinics

Columbia, Missouri, United States

Site Status

Cardinal Glennon Children's Hospital

St Louis, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Norris Cotton Cancer Center

Lebanon, New Hampshire, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

University of New Mexico School of Medicine

Albuquerque, New Mexico, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

State University of New York Health Sciences Center - Stony Brook

Stony Brook, New York, United States

Site Status

State University of New York - Upstate Medical University

Syracuse, New York, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Oklahoma Memorial Hospital

Oklahoma City, Oklahoma, United States

Site Status

Natalie Warren Bryant Cancer Center

Tulsa, Oklahoma, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

James H. Quillen College of Medicine

Johnson City, Tennessee, United States

Site Status

Saint Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

Simmons Cancer Center - Dallas

Dallas, Texas, United States

Site Status

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, United States

Site Status

University of Texas Medical Branch

Galveston, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

San Antonio Military Pediatric Cancer and Blood Disorders Center

Lackland Air Force Base, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Scott and White Clinic

Temple, Texas, United States

Site Status

Vermont Cancer Center

Burlington, Vermont, United States

Site Status

Inova Fairfax Hospital

Falls Church, Virginia, United States

Site Status

Carilion Roanoke Memorial Hospital

Roanoke, Virginia, United States

Site Status

Madigan Army Medical Center

Tacoma, Washington, United States

Site Status

West Virginia University Medical School, Charleston Division

Charleston, West Virginia, United States

Site Status

West Virginia University Hospitals

Morgantown, West Virginia, United States

Site Status

St. Vincent Hospital

Green Bay, Wisconsin, United States

Site Status

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Alberta Children's Hospital

Calgary, Alberta, Canada

Site Status

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Montreal Children's Hospital

Montreal, Quebec, Canada

Site Status

Hopital Sainte Justine

Montreal, Quebec, Canada

Site Status

Centre Hospitalier de L'Universite Laval

Sainte-Foy, Quebec, Canada

Site Status

Academisch Ziekenhuis Groningen

Groningen, , Netherlands

Site Status

San Jorge Childrens Hospital

Santurce, , Puerto Rico

Site Status

Clinique de Pediatrie

Geneva, , Switzerland

Site Status

Countries

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United States Canada Netherlands Puerto Rico Switzerland

Other Identifiers

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POG-9879

Identifier Type: -

Identifier Source: secondary_id

CDR0000066706

Identifier Type: -

Identifier Source: secondary_id

9879

Identifier Type: -

Identifier Source: org_study_id

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