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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT00107471
Other study ID # ACNS0224
Secondary ID CDR0000417842COG
Status Terminated
Phase Phase 1/Phase 2
First received April 5, 2005
Last updated December 9, 2013
Start date October 2005

Study information

Verified date December 2013
Source Children's Oncology Group
Contact n/a
Is FDA regulated No
Health authority United States: Federal Government
Study type Interventional

Clinical Trial Summary

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.


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.


Recruitment information / eligibility

Status Terminated
Enrollment 7
Est. completion date
Est. primary completion date October 2007
Accepts healthy volunteers No
Gender Both
Age group 3 Years to 21 Years
Eligibility 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

Biological:
filgrastim
Given PO
Drug:
topotecan hydrochloride
Given IV
Radiation:
radiation therapy


Locations

Country Name City State
Australia Royal Children's Hospital Herston, Brisbane Queensland
Australia Women's and Children's Hospital North Adelaide South Australia
Australia Princess Margaret Hospital for Children Perth Western Australia
Canada Children's Hospital of Western Ontario London Ontario
Canada Hopital Sainte Justine Montreal Quebec
Canada Montreal Children's Hospital at McGill University Health Center Montreal Quebec
Canada Saskatoon Cancer Centre at the University of Saskatchewan Saskatoon Saskatchewan
Switzerland Swiss Pediatric Oncology Group Bern Bern
United States University of New Mexico Cancer Research and Treatment Center Albuquerque New Mexico
United States Texas Tech University Health Sciences Center School of Medicine - Amarillo Amarillo Texas
United States C.S. Mott Children's Hospital at University of Michigan Medical Center Ann Arbor Michigan
United States CancerCare of Maine at Eastern Maine Medial Center Bangor Maine
United States Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham Birmingham Alabama
United States St. Luke's Mountain States Tumor Institute - Boise Boise Idaho
United States Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston Massachusetts
United States Floating Hospital for Children at Tufts - New England Medical Center Boston Massachusetts
United States Hollings Cancer Center at Medical University of South Carolina Charleston South Carolina
United States West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division Charleston West Virginia
United States Blumenthal Cancer Center at Carolinas Medical Center Charlotte North Carolina
United States Children's Memorial Hospital - Chicago Chicago Illinois
United States University of Chicago Cancer Research Center Chicago Illinois
United States University of Illinois Cancer Center Chicago Illinois
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States Cleveland Clinic Taussig Cancer Center Cleveland Ohio
United States Rainbow Babies and Children's Hospital Cleveland Ohio
United States Palmetto Health South Carolina Cancer Center Columbia South Carolina
United States Columbus Children's Hospital Columbus Ohio
United States Driscoll Children's Hospital Corpus Christi Texas
United States Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas Dallas Texas
United States Children's Medical Center - Dayton Dayton Ohio
United States Barbara Ann Karmanos Cancer Institute Detroit Michigan
United States Southern California Permanente Medical Group Downey California
United States Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center Farmington Connecticut
United States Lee Cancer Care of Lee Memorial Health System Fort Myers Florida
United States Cook Children's Medical Center - Fort Worth Fort Worth Texas
United States University of Florida Shands Cancer Center Gainesville Florida
United States Spectrum Health Hospital - Butterworth Campus Grand Rapids Michigan
United States Hackensack University Medical Center Cancer Center Hackensack New Jersey
United States Penn State Cancer Institute at Milton S. Hershey Medical Center Hershey Pennsylvania
United States Cancer Research Center of Hawaii Honolulu Hawaii
United States Edwards Comprehensive Cancer Center at Cabell Huntington Hospital Huntington West Virginia
United States Indiana University Cancer Center Indianapolis Indiana
United States University of Mississippi Medical Center Jackson Mississippi
United States Nemours Children's Clinic Jacksonville Florida
United States CCOP - Kalamazoo Kalamazoo Michigan
United States Children's Mercy Hospital Kansas City Missouri
United States Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center Kansas City Kansas
United States Sunrise Hospital and Medical Center Las Vegas Nevada
United States Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center Lebanon New Hampshire
United States Arkansas Cancer Research Center at University of Arkansas for Medical Sciences Little Rock Arkansas
United States Kosair Children's Hospital Louisville Kentucky
United States Children's Hospital Central California Madera California
United States University of Miami Sylvester Comprehensive Cancer Center Miami Florida
United States Midwest Children's Cancer Center Milwaukee Wisconsin
United States Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis Minnesota
United States University of Minnesota Medical Center & Children's Hospital - Fairview Minneapolis Minnesota
United States Overlook Hospital Morristown New Jersey
United States Vanderbilt-Ingram Cancer Center Nashville Tennessee
United States Herbert Irving Comprehensive Cancer Center at Columbia University New York New York
United States NYU Cancer Institute at New York University Medical Center New York New York
United States Advocate Christ Medical Center Oak Lawn Illinois
United States Oklahoma University Cancer Institute Oklahoma City Oklahoma
United States Children's Hospital of Orange County Orange California
United States Florida Hospital Cancer Institute at Florida Hospital Orlando Orlando Florida
United States Nemours Children's Clinic - Orlando Orlando Florida
United States Sacred Heart Cancer Center at Sacred Heart Hospital Pensacola Florida
United States Saint Jude Midwest Affiliate Peoria Illinois
United States Phoenix Children's Hospital Phoenix Arizona
United States Children's Hospital of Pittsburgh Pittsburgh Pennsylvania
United States James P. Wilmot Cancer Center at University of Rochester Medical Center Rochester New York
United States Mayo Clinic Cancer Center Rochester Minnesota
United States Sutter Cancer Center Sacramento California
United States Primary Children's Medical Center Salt Lake City Utah
United States Methodist Children's Hospital of South Texas San Antonio Texas
United States Providence Cancer Center at Sacred Heart Medical Center Spokane Washington
United States Siteman Cancer Center at Barnes-Jewish Hospital St. Louis Missouri
United States Stanford Comprehensive Cancer Center - Stanford Stanford California
United States SUNY Upstate Medical University Hospital Syracuse New York
United States St. Joseph's Cancer Institute at St. Joseph's Hospital Tampa Florida
United States New York Medical College Valhalla New York

Sponsors (2)

Lead Sponsor Collaborator
Children's Oncology Group National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Switzerland, 

Outcome

Type Measure Description Time frame Safety issue
Primary Time to treatment failure (e.g., tumor progression, tumor recurrence, or death from any cause) 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 No
Secondary Time to death From the time of study entry to the first occurrence of death by any cause Yes
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