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

This study has been 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).)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00107471
First received: April 5, 2005
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Brain Tumors
Central Nervous System Tumors
Biological: filgrastim
Drug: topotecan hydrochloride
Radiation: radiation therapy
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to death [ Time Frame: From the time of study entry to the first occurrence of death by any cause ] [ Designated as safety issue: Yes ]

Enrollment: 7
Study Start Date: October 2005
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
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.
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.)
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.

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.

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00107471

  Show 80 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Patricia L. Robertson, MD University of Michigan Cancer Center
Study Chair: Richard A. Axtell, MD Helen DeVos Children's Hospital at Spectrum Health
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00107471     History of Changes
Other Study ID Numbers: ACNS0224, CDR0000417842, COG-ACNS0224
Study First Received: April 5, 2005
Last Updated: December 9, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
untreated childhood brain stem glioma

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Lenograstim
Topotecan
Adjuvants, Immunologic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 21, 2014