Topotecan, G-CSF, and Radiation Therapy in Treating Young Patients With Newly Diagnosed Brain Stem Glioma

This study has been terminated.
(The unpromising experience of the French group with topotecan given at a dosage of 0.4 mg/m2/day over 30 mins w/in 1 hr of radiation (Cancer 2005; 104: 2792).)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00107471
First received: April 5, 2005
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as G-CSF, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Radiation therapy uses high-energy x-rays to kill tumor cells. Topotecan may make tumor cells more sensitive to radiation therapy . Giving topotecan and G-CSF together with radiation therapy may be an effective treatment for brain stem glioma.

PURPOSE: This phase I/II trial is studying the side effects and best dose of topotecan when given together with G-CSF and radiation therapy and to see how well they work in treating young patients with newly diagnosed brain stem glioma.


Condition Intervention Phase
Brain Tumors
Central Nervous System Tumors
Biological: filgrastim
Drug: topotecan hydrochloride
Radiation: radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Topotecan With G-CSF and Radiation Therapy in Children With Malignant Intrinsic Pontine Brainstem Gliomas of Childhood

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Time to treatment failure (e.g., tumor progression, tumor recurrence, or death from any cause) [ Time Frame: From date of enrollment until the first occurrence of relapse, progressive disease, secondary malignancy, or death or until last contact if none of these events occur, assessed up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to death [ Time Frame: From the time of study entry to the first occurrence of death by any cause ] [ Designated as safety issue: Yes ]

Enrollment: 7
Study Start Date: October 2005
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Level I (0.5 mg/m^2)
Radiation Therapy + Topotecan hydrochloride daily before each dose of irradiation (radiation therapy) + filgrastim (G-CSF) (p.r.n)
Biological: filgrastim
Given PO
Other Names:
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC #614629
Drug: topotecan hydrochloride
Given IV
Other Names:
  • SKF-104864
  • Hycamtin
  • NSC #609699
Radiation: radiation therapy
Other Names:
  • Conformal therapy or Intensity modulated radiation therapy (IMRT) may be
  • used.
Experimental: Dose Level 2 (0.6 mg/m^2)
Radiation Therapy + Topotecan hydrochloride daily before each dose of irradiation (radiation therapy) + filgrastim (G-CSF) (p.r.n.)
Biological: filgrastim
Given PO
Other Names:
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC #614629
Drug: topotecan hydrochloride
Given IV
Other Names:
  • SKF-104864
  • Hycamtin
  • NSC #609699
Radiation: radiation therapy
Other Names:
  • Conformal therapy or Intensity modulated radiation therapy (IMRT) may be
  • used.

Detailed Description:

OBJECTIVES:

Primary

  • Determine the feasibility of escalating the dose of topotecan when administered with filgrastim (G-CSF) and radiotherapy, in terms of increasing the topotecan dose 25-50% above the maximum tolerated dose (MTD) determined in a prior phase I study, in young patients with newly diagnosed malignant intrinsic pontine brain stem glioma. (Phase I)
  • Determine the dose-limiting toxic effects of topotecan in these patients. (Phase I)
  • Determine the 1-year event-free survival and overall survival of patients treated with this regimen (at the MTD of topotecan determined in phase I). (Phase II)
  • Determine the toxicity of this regimen in these patients. (Phase II)

Secondary

  • Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a multicenter, phase I, dose-escalation study of topotecan followed by a phase II study.

  • Phase I: Patients receive topotecan IV over 30 minutes followed by radiotherapy once daily, 5 days a week for 6-7 weeks. During chemoradiotherapy, patients also receive filgrastim (G-CSF) IV or subcutaneously daily, if needed, until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 out of 6 patients experience dose-limiting toxicity.

  • Phase II: Patients receive topotecan (at the MTD determined in phase I ), G-CSF, and radiotherapy as in phase I.

After completion of study treatment, patients are followed within 2 weeks, every 3 months for 1.5 years, every 6 months for 1.5 years, and then annually until disease relapse.

PROJECTED ACCRUAL: A total of 3-72 patients (3-12 for phase I and 60 for phase II) will be accrued for this study within approximately 3 years.

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of intrinsic pontine brain stem glioma within the past 30 days

    • Histologic confirmation not required provided the tumor has a pontine epicenter AND exhibits diffuse (rather than focal) involvement of ≥ 2/3 of the pons with or without extension to the adjacent medulla or midbrain* NOTE: *Brain stem tumors that do not meet these criteria must be histologically confirmed as grade III or IV malignant glioma
  • Measurable disease by radiographic imaging

    • Post-operative MRI required within the past 30 days if patient had a biopsy or surgical resection
  • No disseminated disease
  • No neurofibromatosis type 1

PATIENT CHARACTERISTICS:

Age

  • 3 to 21 at diagnosis

Performance status

  • Lansky 50-100% OR
  • Karnofsky 50-100%

Life expectancy

  • At least 8 weeks

Hematopoietic

  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3 (transfusion independent)
  • Hemoglobin ≥ 10.0 g/dL (transfusion allowed)

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT < 2.5 times ULN

Renal

  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR
  • Creatinine based on age as follows:

    • No greater than 0.8 mg/dL (for patients ≤ 5 years of age)
    • No greater than 1.0 mg/dL (for patients 6 to 10 years of age)
    • No greater than 1.2 mg/dL (for patients 11 to 15 years of age)
    • No greater than 1.5 mg/dL (for patients over 15 years of age)

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Not severely somnolent or comatose

    • Central cortical neurotoxicity scale < grade 3

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent immunomodulating agents

Chemotherapy

  • No other concurrent anticancer chemotherapy

Endocrine therapy

  • Concurrent corticosteroids allowed for neurological deficits related to the tumor

Radiotherapy

  • No prior radiotherapy

Surgery

  • See Disease Characteristics
  • Prior biopsy or surgical resection for malignant brain stem glioma allowed

Other

  • No other prior therapy for malignant brain stem glioma
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00107471

  Hide Study Locations
Locations
United States, Alabama
Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016-7710
United States, Arkansas
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Southern California Permanente Medical Group
Downey, California, United States, 90242-2814
Children's Hospital Central California
Madera, California, United States, 93638-8762
Children's Hospital of Orange County
Orange, California, United States, 92868
Sutter Cancer Center
Sacramento, California, United States, 95816
Stanford Comprehensive Cancer Center - Stanford
Stanford, California, United States, 94305
United States, Connecticut
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
Farmington, Connecticut, United States, 06360-2875
United States, Florida
Lee Cancer Care of Lee Memorial Health System
Fort Myers, Florida, United States, 33901
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0232
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Florida Hospital Cancer Institute at Florida Hospital Orlando
Orlando, Florida, United States, 32803-1273
Nemours Children's Clinic - Orlando
Orlando, Florida, United States, 32806
Sacred Heart Cancer Center at Sacred Heart Hospital
Pensacola, Florida, United States, 32504
St. Joseph's Cancer Institute at St. Joseph's Hospital
Tampa, Florida, United States, 33607
United States, Hawaii
Cancer Research Center of Hawaii
Honolulu, Hawaii, United States, 95813
United States, Idaho
St. Luke's Mountain States Tumor Institute - Boise
Boise, Idaho, United States, 83712-6297
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
University of Illinois Cancer Center
Chicago, Illinois, United States, 60612-7243
Advocate Christ Medical Center
Oak Lawn, Illinois, United States, 60453
Saint Jude Midwest Affiliate
Peoria, Illinois, United States, 61637
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202-5289
United States, Kansas
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-7357
United States, Kentucky
Kosair Children's Hospital
Louisville, Kentucky, United States, 40232
United States, Maine
CancerCare of Maine at Eastern Maine Medial Center
Bangor, Maine, United States, 04401
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Floating Hospital for Children at Tufts - New England Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
C.S. Mott Children's Hospital at University of Michigan Medical Center
Ann Arbor, Michigan, United States, 48109-0238
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Spectrum Health Hospital - Butterworth Campus
Grand Rapids, Michigan, United States, 49503-2560
CCOP - Kalamazoo
Kalamazoo, Michigan, United States, 49007-5341
United States, Minnesota
University of Minnesota Medical Center & Children's Hospital - Fairview
Minneapolis, Minnesota, United States, 55455
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216-4505
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Siteman Cancer Center at Barnes-Jewish Hospital
St. Louis, Missouri, United States, 63110
United States, Nevada
Sunrise Hospital and Medical Center
Las Vegas, Nevada, United States, 89109-2306
United States, New Hampshire
Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756-0002
United States, New Jersey
Hackensack University Medical Center Cancer Center
Hackensack, New Jersey, United States, 07601
Overlook Hospital
Morristown, New Jersey, United States, 07962
United States, New Mexico
University of New Mexico Cancer Research and Treatment Center
Albuquerque, New Mexico, United States, 87131-5636
United States, New York
Herbert Irving Comprehensive Cancer Center at Columbia University
New York, New York, United States, 10032
NYU Cancer Institute at New York University Medical Center
New York, New York, United States, 10016
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
New York Medical College
Valhalla, New York, United States, 10595
United States, North Carolina
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, United States, 28232-2861
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195-5217
Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106-5000
Columbus Children's Hospital
Columbus, Ohio, United States, 43205-2696
Children's Medical Center - Dayton
Dayton, Ohio, United States, 45404-1815
United States, Oklahoma
Oklahoma University Cancer Institute
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Palmetto Health South Carolina Cancer Center
Columbia, South Carolina, United States, 29203
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6310
United States, Texas
Texas Tech University Health Sciences Center School of Medicine - Amarillo
Amarillo, Texas, United States, 79106
Driscoll Children's Hospital
Corpus Christi, Texas, United States, 78466
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States, 76104-9958
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229-3993
United States, Utah
Primary Children's Medical Center
Salt Lake City, Utah, United States, 84113-1100
United States, Washington
Providence Cancer Center at Sacred Heart Medical Center
Spokane, Washington, United States, 99220-2555
United States, West Virginia
West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division
Charleston, West Virginia, United States, 25302
Edwards Comprehensive Cancer Center at Cabell Huntington Hospital
Huntington, West Virginia, United States, 25701
United States, Wisconsin
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States, 53226
Australia, Queensland
Royal Children's Hospital
Herston, Brisbane, Queensland, Australia, 4029
Australia, South Australia
Women's and Children's Hospital
North Adelaide, South Australia, Australia, 5006
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6001
Canada, Ontario
Children's Hospital of Western Ontario
London, Ontario, Canada, N6A 4G5
Canada, Quebec
Hopital Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
Montreal Children's Hospital at McGill University Health Center
Montreal, Quebec, Canada, H3H 1P3
Canada, Saskatchewan
Saskatoon Cancer Centre at the University of Saskatchewan
Saskatoon, Saskatchewan, Canada, S7N 4H4
Switzerland
Swiss Pediatric Oncology Group Bern
Bern, Switzerland, 3010
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Patricia L. Robertson, MD University of Michigan Cancer Center
Study Chair: Richard A. Axtell, MD Helen DeVos Children's Hospital at Spectrum Health
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00107471     History of Changes
Other Study ID Numbers: ACNS0224, CDR0000417842, COG-ACNS0224
Study First Received: April 5, 2005
Last Updated: December 9, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
untreated childhood brain stem glioma

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Lenograstim
Topotecan
Adjuvants, Immunologic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 21, 2014