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

Brain Tumors Clinical Trial

Official title:

Vincristine, Etoposide and Cyclosporine A in Concert With Standard Dose Radiation Therapy in Diffuse Intrinsic Brain Stem Glioma - A Phase I Study of Dose Escalation of Vincristine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003625
• Other study ID #: 9879
• Secondary ID: POG-9879CDR00000
• Status: Completed
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: July 25, 2014
• Start date: December 1998
• Est. completion date: April 2006

Study information

• Verified date: July 2014
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: April 2006
• Est. primary completion date: February 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 21 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Tumors
• Central Nervous System Neoplasms
• Central Nervous System Tumors
• Nervous System Neoplasms

Intervention

Drug:
• cyclosporine

• etoposide

• vincristine sulfate

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	Montreal Children's Hospital	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Centre Hospitalier de L'Universite Laval	Sainte Foy	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
Netherlands	Academisch Ziekenhuis Groningen	Groningen
Puerto Rico	San Jorge Childrens Hospital	Santurce
Switzerland	Clinique de Pediatrie	Geneva
United States	University of New Mexico School of Medicine	Albuquerque	New Mexico
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Johns Hopkins Oncology Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	University of Alabama Comprehensive Cancer Center	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Floating Hospital for Children	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Vermont Cancer Center	Burlington	Vermont
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Medical School, Charleston Division	Charleston	West Virginia
United States	Children's Memorial Hospital, Chicago	Chicago	Illinois
United States	Rush-Presbyterian-St. Luke's Medical Center	Chicago	Illinois
United States	University of Missouri-Columbia Hospital and Clinics	Columbia	Missouri
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	St. John's Hospital and Medical Center	Detroit	Michigan
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Hurley Medical Center	Flint	Michigan
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	University of Texas Medical Branch	Galveston	Texas
United States	St. Vincent Hospital	Green Bay	Wisconsin
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	James H. Quillen College of Medicine	Johnson City	Tennessee
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Keesler Medical Center - Keesler AFB	Keesler AFB	Mississippi
United States	University of California San Diego Cancer Center	La Jolla	California
United States	San Antonio Military Pediatric Cancer and Blood Disorders Center	Lackland Air Force Base	Texas
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Saint Jude Children's Research Hospital	Memphis	Tennessee
United States	Baptist Hospital of Miami	Miami	Florida
United States	Sylvester Cancer Center, University of Miami	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	West Virginia University Hospitals	Morgantown	West Virginia
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Christ Hospital	Oak Lawn	Illinois
United States	Oklahoma Memorial Hospital	Oklahoma City	Oklahoma
United States	Walt Disney Memorial Cancer Institute	Orlando	Florida
United States	Lucile Packard Children's Hospital at Stanford	Palo Alto	California
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	Maine Children's Cancer Program	Portland	Maine
United States	Carilion Roanoke Memorial Hospital	Roanoke	Virginia
United States	Sutter Cancer Center	Sacramento	California
United States	Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Kaiser Permanente-Southern California Permanente Medical Group	San Diego	California
United States	Naval Medical Center - San Diego	San Diego	California
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	State University of New York Health Sciences Center - Stony Brook	Stony Brook	New York
United States	State University of New York - Upstate Medical University	Syracuse	New York
United States	Madigan Army Medical Center	Tacoma	Washington
United States	Scott and White Clinic	Temple	Texas
United States	Arizona Cancer Center	Tucson	Arizona
United States	Natalie Warren Bryant Cancer Center	Tulsa	Oklahoma
United States	St. Mary's Hospital	West Palm Beach	Florida
United States	Via Christi Regional Medical Center-Saint Francis Campus	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Netherlands,  Puerto Rico,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event Free Survival			Yes