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A Phase I/II Study of Topotecan With G-CSF and Radiation Therapy in Children With Malignant Intrinsic Pontine Brainstem Gliomas of Childhood


Phase 1/Phase 2
3 Years
21 Years
Not Enrolling
Both
Brain and Central Nervous System Tumors

Thank you

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 CenterRochester, Minnesota  55905
University of Chicago Cancer Research CenterChicago, Illinois  60637
Indiana University Cancer CenterIndianapolis, Indiana  46202-5265
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Midwest Children's Cancer CenterMilwaukee, Wisconsin  53226
CCOP - KalamazooKalamazoo, Michigan  49007-3731
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health CenterFarmington, Connecticut  06360-2875
Penn State Cancer Institute at Milton S. Hershey Medical CenterHershey, Pennsylvania  17033-0850
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
New York Medical CollegeValhalla, New York  10595
University of Miami Sylvester Comprehensive Cancer CenterMiami, Florida  33136
Siteman Cancer Center at Barnes-Jewish HospitalSaint Louis, Missouri  63110
Cancer Research Center of HawaiiHonolulu, Hawaii  96813
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
Sutter Cancer CenterSacramento, California  95816
Children's Hospital of Orange CountyOrange, California  92668
Children's Mercy HospitalKansas City, Missouri  64108
Children's Hospital of PittsburghPittsburgh, Pennsylvania  15213
Nemours Children's ClinicJacksonville, Florida  32207
Children's Memorial Hospital - ChicagoChicago, Illinois  60614
Saint Jude Midwest AffiliatePeoria, Illinois  61637
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBoston, Massachusetts  02115
University of New Mexico Cancer Research and Treatment CenterAlbuquerque, New Mexico  87131
Driscoll Children's HospitalCorpus Christi, Texas  78466
Cook Children's Medical Center - Fort WorthFort Worth, Texas  76104
Phoenix Children's HospitalPhoenix, Arizona  85016-7710
Southern California Permanente Medical GroupDowney, California  90242
Children's Hospital Central CaliforniaMadera, California  93638-8762
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Sunrise Hospital and Medical CenterLas Vegas, Nevada  89109-2306
Children's Medical Center - DaytonDayton, Ohio  45404
Palmetto Health South Carolina Cancer CenterColumbia, South Carolina  29203
Arkansas Cancer Research Center at University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Kansas Masonic Cancer Research Institute at the University of Kansas Medical CenterKansas City, Kansas  66160-7353
Herbert Irving Comprehensive Cancer Center at Columbia UniversityNew York, New York  10032
Blumenthal Cancer Center at Carolinas Medical CenterCharlotte, North Carolina  28232-2861
Overlook HospitalSummit, New Jersey  07902-0220
Lee Cancer Care of Lee Memorial Health SystemFort Myers, Florida  33901
University of Florida Shands Cancer CenterGainesville, Florida  32610-0232
Nemours Children's Clinic - OrlandoOrlando, Florida  32806
Florida Hospital Cancer Institute at Florida Hospital OrlandoOrlando, Florida  32803-1273
Sacred Heart Cancer Center at Sacred Heart HospitalPensacola, Florida  32504
St. Joseph's Cancer Institute at St. Joseph's HospitalTampa, Florida  33607
St. Luke's Mountain States Tumor Institute - BoiseBoise, Idaho  83712-6297
Advocate Christ Medical CenterOak Lawn, Illinois  60453
CancerCare of Maine at Eastern Maine Medial CenterBangor, Maine  04401
Floating Hospital for Children at Tufts - New England Medical CenterBoston, Massachusetts  02111
Hackensack University Medical Center Cancer CenterHackensack, New Jersey  07601
NYU Cancer Institute at New York University Medical CenterNew York, New York  10016
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Rainbow Babies and Children's HospitalCleveland, Ohio  44106-5000
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
Texas Tech University Health Sciences Center School of Medicine - AmarilloAmarillo, Texas  79106
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390
Methodist Children's Hospital of South TexasSan Antonio, Texas  78229-3993
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
Providence Cancer Center at Sacred Heart Medical CenterSpokane, Washington  99220-2555
West Virginia University - Robert C. Byrd Health Sciences Center - Charleston DivisionCharleston, West Virginia  25302
Edwards Comprehensive Cancer Center at Cabell Huntington HospitalHuntington, West Virginia  25701
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
University of Illinois Cancer CenterChicago, Illinois  60612-7243
C.S. Mott Children's Hospital at University of Michigan Medical CenterAnn Arbor, Michigan  48109-0286
Children's Hospitals and Clinics of Minnesota - MinneapolisMinneapolis, Minnesota  55404
Oklahoma University Cancer InstituteOklahoma City, Oklahoma  73104
Spectrum Health Hospital - Butterworth CampusGrand Rapids, Michigan  49503
Columbus Children's HospitalColumbus, Ohio  43205-2696
University of Minnesota Medical Center & Children's Hospital - FairviewMinneapolis, Minnesota  55455
Stanford Comprehensive Cancer Center - StanfordStanford, California  94305
Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical CenterLebanon, New Hampshire  03756-0002
Lurleen Wallace Comprehensive Cancer at University of Alabama-BirminghamBirmingham, Alabama  35294