A Phase I/II Study of Topotecan With G-CSF and Radiation Therapy in Children With Malignant Intrinsic Pontine Brainstem Gliomas of Childhood
3 Years
21 Years
Both
Brain and Central Nervous System Tumors
Trial Information
A Phase I/II Study of Topotecan With G-CSF and Radiation Therapy in Children With Malignant Intrinsic Pontine Brainstem Gliomas of Childhood
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.
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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Outcome Measure:
Time to treatment failure (e.g., tumor progression, tumor recurrence, or death from any cause)
Safety Issue:
No
Principal Investigator
Patricia L. Robertson, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of Michigan Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000417842
NCT ID:
NCT00107471
Start Date:
October 2005
Completion Date:
Related Keywords:
- Brain and Central Nervous System Tumors
- untreated childhood brain stem glioma
- Glioma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
Name | Location |
|---|---|
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
| University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
| Indiana University Cancer Center | Indianapolis, Indiana 46202-5265 |
| Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
| University of Mississippi Medical Center | Jackson, Mississippi 39216-4505 |
| Midwest Children's Cancer Center | Milwaukee, Wisconsin 53226 |
| CCOP - Kalamazoo | Kalamazoo, Michigan 49007-3731 |
| Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center | Farmington, Connecticut 06360-2875 |
| Penn State Cancer Institute at Milton S. Hershey Medical Center | Hershey, Pennsylvania 17033-0850 |
| Vanderbilt-Ingram Cancer Center | Nashville, Tennessee 37232-6838 |
| New York Medical College | Valhalla, New York 10595 |
| University of Miami Sylvester Comprehensive Cancer Center | Miami, Florida 33136 |
| Siteman Cancer Center at Barnes-Jewish Hospital | Saint Louis, Missouri 63110 |
| Cancer Research Center of Hawaii | Honolulu, Hawaii 96813 |
| Cleveland Clinic Taussig Cancer Center | Cleveland, Ohio 44195 |
| Sutter Cancer Center | Sacramento, California 95816 |
| Children's Hospital of Orange County | Orange, California 92668 |
| Children's Mercy Hospital | Kansas City, Missouri 64108 |
| Children's Hospital of Pittsburgh | Pittsburgh, Pennsylvania 15213 |
| Nemours Children's Clinic | Jacksonville, Florida 32207 |
| Children's Memorial Hospital - Chicago | Chicago, Illinois 60614 |
| Saint Jude Midwest Affiliate | Peoria, Illinois 61637 |
| Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute | Boston, Massachusetts 02115 |
| University of New Mexico Cancer Research and Treatment Center | Albuquerque, New Mexico 87131 |
| Driscoll Children's Hospital | Corpus Christi, Texas 78466 |
| Cook Children's Medical Center - Fort Worth | Fort Worth, Texas 76104 |
| Phoenix Children's Hospital | Phoenix, Arizona 85016-7710 |
| Southern California Permanente Medical Group | Downey, California 90242 |
| Children's Hospital Central California | Madera, California 93638-8762 |
| Kosair Children's Hospital | Louisville, Kentucky 40202-3830 |
| Sunrise Hospital and Medical Center | Las Vegas, Nevada 89109-2306 |
| Children's Medical Center - Dayton | Dayton, Ohio 45404 |
| Palmetto Health South Carolina Cancer Center | Columbia, South Carolina 29203 |
| Arkansas Cancer Research Center at University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
| Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center | Kansas City, Kansas 66160-7353 |
| Herbert Irving Comprehensive Cancer Center at Columbia University | New York, New York 10032 |
| Blumenthal Cancer Center at Carolinas Medical Center | Charlotte, North Carolina 28232-2861 |
| Overlook Hospital | Summit, New Jersey 07902-0220 |
| Lee Cancer Care of Lee Memorial Health System | Fort Myers, Florida 33901 |
| University of Florida Shands Cancer Center | Gainesville, Florida 32610-0232 |
| Nemours Children's Clinic - Orlando | Orlando, Florida 32806 |
| Florida Hospital Cancer Institute at Florida Hospital Orlando | Orlando, Florida 32803-1273 |
| Sacred Heart Cancer Center at Sacred Heart Hospital | Pensacola, Florida 32504 |
| St. Joseph's Cancer Institute at St. Joseph's Hospital | Tampa, Florida 33607 |
| St. Luke's Mountain States Tumor Institute - Boise | Boise, Idaho 83712-6297 |
| Advocate Christ Medical Center | Oak Lawn, Illinois 60453 |
| CancerCare of Maine at Eastern Maine Medial Center | Bangor, Maine 04401 |
| Floating Hospital for Children at Tufts - New England Medical Center | Boston, Massachusetts 02111 |
| Hackensack University Medical Center Cancer Center | Hackensack, New Jersey 07601 |
| NYU Cancer Institute at New York University Medical Center | New York, New York 10016 |
| SUNY Upstate Medical University Hospital | Syracuse, New York 13210 |
| Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio 45229-3039 |
| Rainbow Babies and Children's Hospital | Cleveland, Ohio 44106-5000 |
| Hollings Cancer Center at Medical University of South Carolina | Charleston, South Carolina 29425 |
| Texas Tech University Health Sciences Center School of Medicine - Amarillo | Amarillo, Texas 79106 |
| Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas | Dallas, Texas 75390 |
| Methodist Children's Hospital of South Texas | San Antonio, Texas 78229-3993 |
| Primary Children's Medical Center | Salt Lake City, Utah 84113-1100 |
| Providence Cancer Center at Sacred Heart Medical Center | Spokane, Washington 99220-2555 |
| West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division | Charleston, West Virginia 25302 |
| Edwards Comprehensive Cancer Center at Cabell Huntington Hospital | Huntington, West Virginia 25701 |
| James P. Wilmot Cancer Center at University of Rochester Medical Center | Rochester, New York 14642 |
| University of Illinois Cancer Center | Chicago, Illinois 60612-7243 |
| C.S. Mott Children's Hospital at University of Michigan Medical Center | Ann Arbor, Michigan 48109-0286 |
| Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis, Minnesota 55404 |
| Oklahoma University Cancer Institute | Oklahoma City, Oklahoma 73104 |
| Spectrum Health Hospital - Butterworth Campus | Grand Rapids, Michigan 49503 |
| Columbus Children's Hospital | Columbus, Ohio 43205-2696 |
| University of Minnesota Medical Center & Children's Hospital - Fairview | Minneapolis, Minnesota 55455 |
| Stanford Comprehensive Cancer Center - Stanford | Stanford, California 94305 |
| Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center | Lebanon, New Hampshire 03756-0002 |
| Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham | Birmingham, Alabama 35294 |
