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

Primary Purpose

Brain Tumors, Central Nervous System Tumors

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
cyclosporine
etoposide
vincristine sulfate
radiation therapy
Sponsored by
Children's Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Tumors focused on measuring untreated childhood brain stem glioma

Eligibility Criteria

3 Years - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama Comprehensive Cancer Center
  • Arizona Cancer Center
  • University of Arkansas for Medical Sciences
  • University of California San Diego Cancer Center
  • Lucile Packard Children's Hospital at Stanford
  • Sutter Cancer Center
  • Kaiser Permanente-Southern California Permanente Medical Group
  • Naval Medical Center - San Diego
  • Kaiser Permanente Medical Center - Santa Clara
  • Nemours Children's Clinic
  • Sylvester Cancer Center, University of Miami
  • Baptist Hospital of Miami
  • Walt Disney Memorial Cancer Institute
  • St. Mary's Hospital
  • Emory University Hospital - Atlanta
  • Tripler Army Medical Center
  • Rush-Presbyterian-St. Luke's Medical Center
  • Children's Memorial Hospital, Chicago
  • Christ Hospital
  • Saint Jude Midwest Affiliate
  • University of Kansas Medical Center
  • Via Christi Regional Medical Center-Saint Francis Campus
  • Tulane University School of Medicine
  • Eastern Maine Medical Center
  • Maine Children's Cancer Program
  • Johns Hopkins Oncology Center
  • Floating Hospital for Children
  • Massachusetts General Hospital Cancer Center
  • Dana-Farber Cancer Institute
  • Children's Hospital of Michigan
  • St. John's Hospital and Medical Center
  • Hurley Medical Center
  • University of Mississippi Medical Center
  • Keesler Medical Center - Keesler AFB
  • University of Missouri-Columbia Hospital and Clinics
  • Cardinal Glennon Children's Hospital
  • Washington University School of Medicine
  • Norris Cotton Cancer Center
  • Hackensack University Medical Center
  • University of New Mexico School of Medicine
  • Roswell Park Cancer Institute
  • State University of New York Health Sciences Center - Stony Brook
  • State University of New York - Upstate Medical University
  • Duke Comprehensive Cancer Center
  • Oklahoma Memorial Hospital
  • Natalie Warren Bryant Cancer Center
  • Medical University of South Carolina
  • James H. Quillen College of Medicine
  • Saint Jude Children's Research Hospital
  • Medical City Dallas Hospital
  • Simmons Cancer Center - Dallas
  • Cook Children's Medical Center - Fort Worth
  • University of Texas Medical Branch
  • Baylor College of Medicine
  • San Antonio Military Pediatric Cancer and Blood Disorders Center
  • University of Texas Health Science Center at San Antonio
  • Scott and White Clinic
  • Vermont Cancer Center
  • Inova Fairfax Hospital
  • Carilion Roanoke Memorial Hospital
  • Madigan Army Medical Center
  • West Virginia University Medical School, Charleston Division
  • West Virginia University Hospitals
  • St. Vincent Hospital
  • Midwest Children's Cancer Center
  • Alberta Children's Hospital
  • Children's Hospital of Eastern Ontario
  • Hospital for Sick Children
  • Montreal Children's Hospital
  • Hopital Sainte Justine
  • Centre Hospitalier de L'Universite Laval
  • Academisch Ziekenhuis Groningen
  • San Jorge Childrens Hospital
  • Clinique de Pediatrie

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Stratum 1

Arm Description

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.

Outcomes

Primary Outcome Measures

Event Free Survival

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
July 25, 2014
Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00003625
Brief Title
Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Newly Diagnosed Brain Stem Glioma
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
December 1998 (undefined)
Primary Completion Date
February 2001 (Actual)
Study Completion Date
April 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Tumors, Central Nervous System Tumors
Keywords
untreated childhood brain stem glioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Stratum 1
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Other Intervention Name(s)
CSA, NSC # 290193
Intervention Type
Drug
Intervention Name(s)
etoposide
Other Intervention Name(s)
VP-16, VePesid, NSC # 141540
Intervention Type
Drug
Intervention Name(s)
vincristine sulfate
Other Intervention Name(s)
VCR, Oncovin, NSC # 067574
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Primary Outcome Measure Information:
Title
Event Free Survival

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark L. Greenberg, MD
Organizational Affiliation
The Hospital for Sick Children
Official's Role
Study Chair
Facility Information:
Facility Name
University of Alabama Comprehensive Cancer Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
University of California San Diego Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-0658
Country
United States
Facility Name
Lucile Packard Children's Hospital at Stanford
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Sutter Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
Facility Name
Kaiser Permanente-Southern California Permanente Medical Group
City
San Diego
State/Province
California
ZIP/Postal Code
92120
Country
United States
Facility Name
Naval Medical Center - San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92134-3202
Country
United States
Facility Name
Kaiser Permanente Medical Center - Santa Clara
City
Santa Clara
State/Province
California
ZIP/Postal Code
95051-5386
Country
United States
Facility Name
Nemours Children's Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Sylvester Cancer Center, University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Baptist Hospital of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33176-2197
Country
United States
Facility Name
Walt Disney Memorial Cancer Institute
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
St. Mary's Hospital
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33407
Country
United States
Facility Name
Emory University Hospital - Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Tripler Army Medical Center
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96859-5000
Country
United States
Facility Name
Rush-Presbyterian-St. Luke's Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Children's Memorial Hospital, Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
Christ Hospital
City
Oak Lawn
State/Province
Illinois
ZIP/Postal Code
60453
Country
United States
Facility Name
Saint Jude Midwest Affiliate
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61602
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160-7357
Country
United States
Facility Name
Via Christi Regional Medical Center-Saint Francis Campus
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Tulane University School of Medicine
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Eastern Maine Medical Center
City
Bangor
State/Province
Maine
ZIP/Postal Code
04401
Country
United States
Facility Name
Maine Children's Cancer Program
City
Portland
State/Province
Maine
ZIP/Postal Code
04101
Country
United States
Facility Name
Johns Hopkins Oncology Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Floating Hospital for Children
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Massachusetts General Hospital Cancer Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Children's Hospital of Michigan
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
St. John's Hospital and Medical Center
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48236
Country
United States
Facility Name
Hurley Medical Center
City
Flint
State/Province
Michigan
ZIP/Postal Code
48503
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216-4505
Country
United States
Facility Name
Keesler Medical Center - Keesler AFB
City
Keesler AFB
State/Province
Mississippi
ZIP/Postal Code
39534-2576
Country
United States
Facility Name
University of Missouri-Columbia Hospital and Clinics
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65212
Country
United States
Facility Name
Cardinal Glennon Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Norris Cotton Cancer Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
University of New Mexico School of Medicine
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263-0001
Country
United States
Facility Name
State University of New York Health Sciences Center - Stony Brook
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11790-9832
Country
United States
Facility Name
State University of New York - Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Duke Comprehensive Cancer Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Oklahoma Memorial Hospital
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73126-0307
Country
United States
Facility Name
Natalie Warren Bryant Cancer Center
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74136
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425-0721
Country
United States
Facility Name
James H. Quillen College of Medicine
City
Johnson City
State/Province
Tennessee
ZIP/Postal Code
37614-0622
Country
United States
Facility Name
Saint Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105-2794
Country
United States
Facility Name
Medical City Dallas Hospital
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
Simmons Cancer Center - Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235-9154
Country
United States
Facility Name
Cook Children's Medical Center - Fort Worth
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
University of Texas Medical Branch
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555-1329
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
San Antonio Military Pediatric Cancer and Blood Disorders Center
City
Lackland Air Force Base
State/Province
Texas
ZIP/Postal Code
78236-5300
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78284
Country
United States
Facility Name
Scott and White Clinic
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
Vermont Cancer Center
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401-3498
Country
United States
Facility Name
Inova Fairfax Hospital
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22046
Country
United States
Facility Name
Carilion Roanoke Memorial Hospital
City
Roanoke
State/Province
Virginia
ZIP/Postal Code
24029
Country
United States
Facility Name
Madigan Army Medical Center
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98431-5000
Country
United States
Facility Name
West Virginia University Medical School, Charleston Division
City
Charleston
State/Province
West Virginia
ZIP/Postal Code
25304
Country
United States
Facility Name
West Virginia University Hospitals
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506-9162
Country
United States
Facility Name
St. Vincent Hospital
City
Green Bay
State/Province
Wisconsin
ZIP/Postal Code
54307-3508
Country
United States
Facility Name
Midwest Children's Cancer Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Alberta Children's Hospital
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2T 5C7
Country
Canada
Facility Name
Children's Hospital of Eastern Ontario
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L1
Country
Canada
Facility Name
Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
Montreal Children's Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3H 1P3
Country
Canada
Facility Name
Hopital Sainte Justine
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada
Facility Name
Centre Hospitalier de L'Universite Laval
City
Sainte Foy
State/Province
Quebec
ZIP/Postal Code
GIV 4G2
Country
Canada
Facility Name
Academisch Ziekenhuis Groningen
City
Groningen
ZIP/Postal Code
9713 EZ
Country
Netherlands
Facility Name
San Jorge Childrens Hospital
City
Santurce
ZIP/Postal Code
00912
Country
Puerto Rico
Facility Name
Clinique de Pediatrie
City
Geneva
ZIP/Postal Code
1211
Country
Switzerland

12. IPD Sharing Statement

Learn more about this trial

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

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