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

July 25, 2014 updated by: Children's Oncology Group

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2T 5C7
        • Alberta Children's Hospital
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L1
        • Children's Hospital of Eastern Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children
    • Quebec
      • Montreal, Quebec, Canada, H3H 1P3
        • Montreal Children's Hospital
      • Montreal, Quebec, Canada, H3T 1C5
        • Hopital Sainte Justine
      • 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
      • Geneva, Switzerland, 1211
        • Clinique de Pediatrie
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama Comprehensive Cancer Center
    • 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
      • San Diego, California, United States, 92120
        • Kaiser Permanente-Southern California Permanente Medical Group
      • San Diego, California, United States, 92134-3202
        • Naval Medical Center - San Diego
      • Santa Clara, California, United States, 95051-5386
        • Kaiser Permanente Medical Center - Santa Clara
    • 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
      • Orlando, Florida, United States, 32803
        • Walt Disney Memorial Cancer Institute
      • 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
    • 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
        • Christ Hospital
      • Peoria, Illinois, United States, 61602
        • Saint Jude Midwest Affiliate
    • Kansas
      • Kansas City, Kansas, United States, 66160-7357
        • University of Kansas Medical Center
      • Wichita, Kansas, United States, 67214
        • Via Christi Regional Medical Center-Saint Francis Campus
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University School of Medicine
    • 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, 21287
        • 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
        • Floating Hospital for Children
    • 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
        • Norris Cotton Cancer Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • 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
      • Stony Brook, New York, United States, 11790-9832
        • 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
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73126-0307
        • Oklahoma Memorial Hospital
      • Tulsa, Oklahoma, United States, 74136
        • Natalie Warren Bryant Cancer Center
    • South Carolina
      • Charleston, South Carolina, United States, 29425-0721
        • Medical University of South Carolina
    • 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
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center - Fort Worth
      • Galveston, Texas, United States, 77555-1329
        • 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
        • University of Texas Health Science Center at San Antonio
      • Temple, Texas, United States, 76508
        • Scott and White Clinic
    • Vermont
      • Burlington, Vermont, United States, 05401-3498
        • Vermont Cancer Center
    • Virginia
      • Falls Church, Virginia, United States, 22046
        • Inova Fairfax Hospital
      • Roanoke, Virginia, United States, 24029
        • Carilion Roanoke Memorial 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 Division
      • 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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Radiation: radiation therapy
Drug: etoposide
Other Names:
  • VP-16
  • VePesid
  • NSC # 141540
Drug: vincristine sulfate
Other Names:
  • VCR
  • Oncovin
  • NSC # 067574
Drug: cyclosporine
Other Names:
  • CSA
  • NSC # 290193

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Event Free Survival

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Mark L. Greenberg, MD, The Hospital for Sick Children

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 1998

Primary Completion (Actual)

February 1, 2001

Study Completion (Actual)

April 1, 2006

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

September 10, 2004

First Posted (Estimate)

September 13, 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

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 9879
  • POG-9879
  • CDR0000066706

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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