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

NCT ID: NCT00107471

Last Updated: 2013-12-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

7 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-10-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Brain Tumors Central Nervous System Tumors

Keywords

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untreated childhood brain stem glioma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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)

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

Given PO

topotecan hydrochloride

Intervention Type DRUG

Given IV

radiation therapy

Intervention Type RADIATION

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.)

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

Given PO

topotecan hydrochloride

Intervention Type DRUG

Given IV

radiation therapy

Intervention Type RADIATION

Interventions

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filgrastim

Given PO

Intervention Type BIOLOGICAL

topotecan hydrochloride

Given IV

Intervention Type DRUG

radiation therapy

Intervention Type RADIATION

Other Intervention Names

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Granulocyte Colony-Stimulating Factor r-metHuG-CSF G-CSF Neupogen NSC #614629 SKF-104864 Hycamtin NSC #609699 Conformal therapy or Intensity modulated radiation therapy (IMRT) may be used.

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

3 Years

Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Patricia L. Robertson, MD

Role: STUDY_CHAIR

University of Michigan Rogel Cancer Center

Richard A. Axtell, MD

Role: STUDY_CHAIR

Helen DeVos Children's Hospital at Spectrum Health

Locations

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Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham

Birmingham, Alabama, United States

Site Status

Phoenix Children's Hospital

Phoenix, Arizona, United States

Site Status

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Southern California Permanente Medical Group

Downey, California, United States

Site Status

Children's Hospital Central California

Madera, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

Sutter Cancer Center

Sacramento, California, United States

Site Status

Stanford Comprehensive Cancer Center - Stanford

Stanford, California, United States

Site Status

Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center

Farmington, Connecticut, United States

Site Status

Lee Cancer Care of Lee Memorial Health System

Fort Myers, Florida, United States

Site Status

University of Florida Shands Cancer Center

Gainesville, Florida, United States

Site Status

Nemours Children's Clinic

Jacksonville, Florida, United States

Site Status

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Florida Hospital Cancer Institute at Florida Hospital Orlando

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Orlando

Orlando, Florida, United States

Site Status

Sacred Heart Cancer Center at Sacred Heart Hospital

Pensacola, Florida, United States

Site Status

St. Joseph's Cancer Institute at St. Joseph's Hospital

Tampa, Florida, United States

Site Status

Cancer Research Center of Hawaii

Honolulu, Hawaii, United States

Site Status

St. Luke's Mountain States Tumor Institute - Boise

Boise, Idaho, United States

Site Status

University of Illinois Cancer Center

Chicago, Illinois, United States

Site Status

Children's Memorial Hospital - Chicago

Chicago, Illinois, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

Advocate Christ Medical Center

Oak Lawn, Illinois, United States

Site Status

Saint Jude Midwest Affiliate

Peoria, Illinois, United States

Site Status

Indiana University Cancer Center

Indianapolis, Indiana, United States

Site Status

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Kosair Children's Hospital

Louisville, Kentucky, United States

Site Status

CancerCare of Maine at Eastern Maine Medial Center

Bangor, Maine, United States

Site Status

Floating Hospital for Children at Tufts - New England Medical Center

Boston, Massachusetts, United States

Site Status

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

C.S. Mott Children's Hospital at University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Spectrum Health Hospital - Butterworth Campus

Grand Rapids, Michigan, United States

Site Status

CCOP - Kalamazoo

Kalamazoo, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

Site Status

University of Minnesota Medical Center & Children's Hospital - Fairview

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status

Sunrise Hospital and Medical Center

Las Vegas, Nevada, United States

Site Status

Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, United States

Site Status

Overlook Hospital

Morristown, New Jersey, United States

Site Status

University of New Mexico Cancer Research and Treatment Center

Albuquerque, New Mexico, United States

Site Status

NYU Cancer Institute at New York University Medical Center

New York, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center at Columbia University

New York, New York, United States

Site Status

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, United States

Site Status

SUNY Upstate Medical University Hospital

Syracuse, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Columbus Children's Hospital

Columbus, Ohio, United States

Site Status

Children's Medical Center - Dayton

Dayton, Ohio, United States

Site Status

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, United States

Site Status

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Palmetto Health South Carolina Cancer Center

Columbia, South Carolina, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Texas Tech University Health Sciences Center School of Medicine - Amarillo

Amarillo, Texas, United States

Site Status

Driscoll Children's Hospital

Corpus Christi, Texas, United States

Site Status

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, United States

Site Status

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, United States

Site Status

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States

Site Status

Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status

Providence Cancer Center at Sacred Heart Medical Center

Spokane, Washington, United States

Site Status

West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division

Charleston, West Virginia, United States

Site Status

Edwards Comprehensive Cancer Center at Cabell Huntington Hospital

Huntington, West Virginia, United States

Site Status

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Royal Children's Hospital

Herston, Brisbane, Queensland, Australia

Site Status

Women's and Children's Hospital

North Adelaide, South Australia, Australia

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

Children's Hospital of Western Ontario

London, Ontario, Canada

Site Status

Montreal Children's Hospital at McGill University Health Center

Montreal, Quebec, Canada

Site Status

Hopital Sainte Justine

Montreal, Quebec, Canada

Site Status

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, Canada

Site Status

Swiss Pediatric Oncology Group Bern

Bern, , Switzerland

Site Status

Countries

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Netherlands New Zealand Puerto Rico United States Australia Canada Switzerland

Other Identifiers

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CDR0000417842

Identifier Type: OTHER

Identifier Source: secondary_id

COG-ACNS0224

Identifier Type: OTHER

Identifier Source: secondary_id

ACNS0224

Identifier Type: -

Identifier Source: org_study_id