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

Brain Tumors Clinical Trial

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

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. 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

Related Conditions & MeSH terms

• Brain Tumors
• Central Nervous System Neoplasms
• Central Nervous System Tumors
• Nervous System Neoplasms

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