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

Treatment of Children With Diffuse Intrinsic Brain Stem Glioma With Standard Dose Irradiation and Vincristine Plus Oral VP-16, A POG Pilot Study

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 drug with radiation therapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of vincristine plus etoposide and radiation therapy in treating children who have newly diagnosed brain stem glioma.

Study Overview

• Status: Completed
• Conditions: Brain Tumors; Central Nervous System Tumors
• Intervention / Treatment: Radiation: radiation therapy; Drug: etoposide; Drug: vincristine sulfate

Detailed Description

OBJECTIVES: I. Evaluate the efficacy of vincristine plus etoposide with concurrent radiotherapy on one year survival in children with newly diagnosed diffuse intrinsic brain stem glioma. II. Assess the toxicity of this regimen in this patient population.

OUTLINE: Induction: Patients receive oral etoposide daily on days 1-21 and vincristine IV on days 1, 8, and 15. Treatment repeats every 4 weeks for 2 courses. Patients receive radiotherapy daily for 6 weeks concurrently with induction chemotherapy. Maintenance: One week after induction therapy, patients receive vincristine IV on days 1 and 8 and oral etoposide daily on days 1-21. Treatment repeats every 4 weeks for 10 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 2 years.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2T 5C7
      • Alberta Children's Hospital
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Children's Hospital
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Hopital Sainte Justine
    • Montreal, Quebec, Canada, H3H 1P3
      • McGill University Health Center - Montreal Children's Hospital
    • Sainte Foy, Quebec, Canada, GIV 4G2
      • Centre Hospitalier de l'Universite Laval
• Netherlands
  • Groningen, Netherlands, 9713 EZ
    • Academisch Ziekenhuis Groningen
• Puerto Rico
  • Santurce, Puerto Rico, 00912
    • San Jorge Childrens Hospital
• Switzerland
  • Bern, Switzerland, CH 3010
    • Swiss Pediatric Oncology Group Bern
  • Geneva, Switzerland, 1211
    • Clinique de Pediatrie
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama at Birmingham Comprehensive Cancer Center
    • Mobile, Alabama, United States, 36688
      • MBCCOP - Gulf Coast
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • La Jolla, California, United States, 92093-0658
      • University of California San Diego Cancer Center
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital at Stanford
    • Sacramento, California, United States, 95816
      • Sutter Cancer Center
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
    • San Diego, California, United States, 92120
      • Kaiser Permanente-Southern California Permanente Medical Group
    • San Diego, California, United States, 92123-4282
      • Children's Hospital and Health Center
    • Santa Clara, California, United States, 95051-5386
      • Kaiser Permanente Medical Center - Santa Clara
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8028
      • Yale Comprehensive Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20307-5000
      • Walter Reed Army Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610-100277
      • Shands Hospital and Clinics, University of Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic
    • Miami, Florida, United States, 33136
      • Sylvester Cancer Center, University of Miami
    • Miami, Florida, United States, 33176-2197
      • Baptist Hospital of Miami
    • Miami, Florida, United States, 33155
      • Miami Children's Hospital
    • Orlando, Florida, United States, 32803
      • Walt Disney Memorial Cancer Institute
    • St. Petersburg, Florida, United States, 33701
      • All Children's Hospital
    • Tampa, Florida, United States, 33682-7757
      • CCOP - Florida Pediatric
    • West Palm Beach, Florida, United States, 33407
      • St. Mary's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital - Atlanta
  • Hawaii
    • Honolulu, Hawaii, United States, 96859-5000
      • Tripler Army Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Cancer Research Center of Hawaii
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush-Presbyterian-St. Luke's Medical Center
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital, Chicago
    • Oak Lawn, Illinois, United States, 60453
      • Hope Children's Hospital
    • Peoria, Illinois, United States, 61637
      • Saint Jude Midwest Affiliate
    • Peoria, Illinois, United States, 61602
      • CCOP - Illinois Oncology Research Association
  • Kansas
    • Kansas City, Kansas, United States, 66160-7357
      • University of Kansas Medical Center
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67214
      • Via Christi Regional Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
    • New Orleans, Louisiana, United States, 70121
      • CCOP - Ochsner
    • New Orleans, Louisiana, United States, 70112
      • MBCCOP - LSU Health Sciences Center
  • Maine
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
    • Portland, Maine, United States, 04101
      • Maine Children's Cancer Program
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Marlene & Stewart Greenebaum Cancer Center, University of Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Johns Hopkins Oncology Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Boston, Massachusetts, United States, 02111
      • Boston Floating Hospital Infants and Children
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
    • Detroit, Michigan, United States, 48236
      • St. John's Hospital and Medical Center
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Medical Center
    • Keesler AFB, Mississippi, United States, 39534-2576
      • Keesler Medical Center - Keesler AFB
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri-Columbia Hospital and Clinics
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63104
      • Cardinal Glennon Children's Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-0002
      • Norris Cotton Cancer Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Hackensack, New Jersey, United States, 07601
      • CCOP - Northern New Jersey
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico School of Medicine
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • New Hyde Park, New York, United States, 11042
      • Schneider Children's Hospital
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • Rochester, New York, United States, 14642
      • University of Rochester Cancer Center
    • Stony Brook, New York, United States, 11790-7775
      • State University of New York Health Sciences Center - Stony Brook
    • Syracuse, New York, United States, 13210
      • State University of New York - Upstate Medical University
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Saint Joseph's Health System
    • Charlotte, North Carolina, United States, 28232-2861
      • Carolinas Medical Center
    • Charlotte, North Carolina, United States, 28233-3549
      • Presbyterian Healthcare
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Greenville, North Carolina, United States, 27858-4354
      • East Carolina University School of Medicine
    • Winston-Salem, North Carolina, United States, 27157-1082
      • Comprehensive Cancer Center at Wake Forest University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73126-0307
      • Oklahoma Memorial Hospital
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • CCOP - Columbia River Program
    • Portland, Oregon, United States, 97227
      • Legacy Emanuel Hospital and Health Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19134-1095
      • St. Christopher's Hospital for Children
  • South Carolina
    • Charleston, South Carolina, United States, 29425-0721
      • Medical University of South Carolina
    • Greenville, South Carolina, United States, 29605
      • Children's Hospital of Greenville Hospital System
  • Tennessee
    • Johnson City, Tennessee, United States, 37614-0622
      • James H. Quillen College of Medicine
    • Memphis, Tennessee, United States, 38105-2794
      • Saint Jude Children's Research Hospital
  • Texas
    • Dallas, Texas, United States, 75230
      • Medical City Dallas Hospital
    • Dallas, Texas, United States, 75235-9154
      • Simmons Cancer Center - Dallas
    • Dallas, Texas, United States, 75230-2503
      • Texas Oncology P.A.
    • Galveston, Texas, United States, 77555-0209
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Lackland Air Force Base, Texas, United States, 78236-5300
      • San Antonio Military Pediatric Cancer and Blood Disorders Center
    • San Antonio, Texas, United States, 78284-7811
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78229-3900
      • MBCCOP - South Texas Pediatric
    • Temple, Texas, United States, 76508
      • Scott and White Clinic
  • Vermont
    • Burlington, Vermont, United States, 05401-3498
      • Vermont Cancer Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Cancer Center at the University of Virginia
    • Falls Church, Virginia, United States, 22046
      • Inova Fairfax Hospital
    • Portsmouth, Virginia, United States, 23708-2197
      • Naval Medical Center, Portsmouth
    • Richmond, Virginia, United States, 23298-0037
      • Massey Cancer Center
    • Roanoke, Virginia, United States, 24029
      • Carilion Roanoke Community Hospital
  • Washington
    • Tacoma, Washington, United States, 98431-5000
      • Madigan Army Medical Center
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • West Virginia University Medical School-Charleston
    • Morgantown, West Virginia, United States, 26506-9162
      • West Virginia University Hospitals
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54307-3508
      • St. Vincent Hospital
    • Milwaukee, Wisconsin, United States, 53226
      • Midwest Children's Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS: Newly diagnosed diffuse intrinsic brain stem glioma by MRI At least 2/3 of the tumor in the pons Tumor origin clearly in the pons At least 2 clinical features with less than 6 months duration: Cranial nerve deficit Long tract signs Ataxia No diffuse brain stem enlargement secondary to neurofibromatosis No diffuse leptomeningeal disease

PATIENT CHARACTERISTICS: Age: 3 to 21 Performance status: Karnofsky or Lansky 50-100% Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin less than 2.0 mg/dL ALT no greater than 5 times upper limit of normal Renal: Creatinine or GFR normal for age

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy Chemotherapy: No other concurrent chemotherapy No prior chemotherapy Endocrine therapy: Prior glucocorticoids allowed Radiotherapy: No prior radiotherapy Surgery: No prior surgery Other: No other concurrent investigational drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment; Induction: Patients receive oral etoposide daily on days 1-21 and vincristine sulfate IV on days 1, 8, and 15. Treatment repeats every 4 weeks for 2 courses. Patients receive radiation therapy daily for 6 weeks concurrently with induction chemotherapy. Maintenance: One week after induction therapy, patients receive vincristine sulfate IV on days 1 and 8 and oral etoposide daily on days 1-21. Treatment repeats every 4 weeks for 10 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter

Radiation: radiation therapy; Drug: etoposide; Other Names: VP-16; VePesid; NSC # 141540; Drug: vincristine sulfate; Other Names: VCR; Oncovin; NSC # 067574

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Survival	1 year

Secondary Outcome Measures

Outcome Measure
Monitor the toxicity

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: David N. Korones, MD, James P. Wilmot Cancer Center

Publications and helpful links

General Publications

• Korones DN, Fisher PG, Kretschmar C, Zhou T, Chen Z, Kepner J, Freeman C. Treatment of children with diffuse intrinsic brain stem glioma with radiotherapy, vincristine and oral VP-16: a Children's Oncology Group phase II study. Pediatr Blood Cancer. 2008 Feb;50(2):227-30. doi: 10.1002/pbc.21154.

Study record dates

Study Major Dates

• Study Start: September 1, 1999
• Primary Completion (Actual): October 1, 2003
• Study Completion (Actual): March 1, 2007

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: February 19, 2004
• First Posted (Estimate): February 20, 2004

Study Record Updates

• Last Update Posted (Estimate): July 28, 2014
• Last Update Submitted That Met QC Criteria: July 25, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: untreated childhood brain stem glioma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Etoposide; Vincristine
• Other Study ID Numbers: 9836; POG-9836 (Other Identifier: Pediatric Oncology Group); CDR0000067127 (Other Identifier: Clinical Trials.gov); COG-P9836 (Other Identifier: Children's Oncology Group)