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

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ClinicalTrials.gov Identifier: NCT00107471
Recruitment Status : Terminated (The unpromising experience of the French group with topotecan given at a dosage of 0.4 mg/m2/day over 30 mins w/in 1 hr of radiation (Cancer 2005; 104: 2792).)
First Posted : April 6, 2005
Last Update Posted : December 10, 2013
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date  ICMJE April 5, 2005
First Posted Date  ICMJE April 6, 2005
Last Update Posted Date December 10, 2013
Study Start Date  ICMJE October 2005
Actual Primary Completion Date October 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 22, 2013)
Time to treatment failure (e.g., tumor progression, tumor recurrence, or death from any cause) [ Time Frame: 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 ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 22, 2013)
Time to death [ Time Frame: From the time of study entry to the first occurrence of death by any cause ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Topotecan, G-CSF, and Radiation Therapy in Treating Young Patients With Newly Diagnosed Brain Stem Glioma
Official Title  ICMJE A Phase I/II Study of Topotecan With G-CSF and Radiation Therapy in Children With Malignant Intrinsic Pontine Brainstem Gliomas of Childhood
Brief 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.

Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Brain Tumors
  • Central Nervous System Tumors
Intervention  ICMJE
  • Biological: filgrastim
    Given PO
    Other Names:
    • Granulocyte Colony-Stimulating Factor
    • r-metHuG-CSF
    • G-CSF
    • Neupogen
    • NSC #614629
  • Drug: topotecan hydrochloride
    Given IV
    Other Names:
    • SKF-104864
    • Hycamtin
    • NSC #609699
  • Radiation: radiation therapy
    Other Names:
    • Conformal therapy or Intensity modulated radiation therapy (IMRT) may be
    • used.
Study Arms  ICMJE
  • Experimental: 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)
    Interventions:
    • Biological: filgrastim
    • Drug: topotecan hydrochloride
    • Radiation: radiation therapy
  • Experimental: 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.)
    Interventions:
    • Biological: filgrastim
    • Drug: topotecan hydrochloride
    • Radiation: radiation therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 22, 2013)
7
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date October 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   Switzerland,   United States
Removed Location Countries Netherlands,   New Zealand,   Puerto Rico
 
Administrative Information
NCT Number  ICMJE NCT00107471
Other Study ID Numbers  ICMJE ACNS0224
CDR0000417842 ( Other Identifier: Clinical Trials.gov )
COG-ACNS0224 ( Other Identifier: Children's Oncology Group )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Oncology Group
Study Sponsor  ICMJE Children's Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Patricia L. Robertson, MD University of Michigan Rogel Cancer Center
Study Chair: Richard A. Axtell, MD Helen DeVos Children's Hospital at Spectrum Health
PRS Account Children's Oncology Group
Verification Date December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP