Topotecan, G-CSF, and Radiation Therapy in Treating Young Patients With Newly Diagnosed Brain Stem Glioma
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| ClinicalTrials.gov Identifier: NCT00107471 |
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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
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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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Brain Tumors Central Nervous System Tumors | Biological: filgrastim Drug: topotecan hydrochloride Radiation: radiation therapy | Phase 1 Phase 2 |
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 : | Interventional (Clinical Trial) |
| Actual Enrollment : | 7 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Single Group Assignment |
| Masking: | None (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 |
| Study Start Date : | October 2005 |
| Actual Primary Completion Date : | October 2007 |
| Arm | Intervention/treatment |
|---|---|
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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)
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Biological: filgrastim
Given PO
Other Names:
Drug: topotecan hydrochloride Given IV
Other Names:
Radiation: radiation therapy Other Names:
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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.)
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Biological: filgrastim
Given PO
Other Names:
Drug: topotecan hydrochloride Given IV
Other Names:
Radiation: radiation therapy Other Names:
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- 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 ]
- Time to death [ Time Frame: From the time of study entry to the first occurrence of death by any cause ]
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| Ages Eligible for Study: | 3 Years to 21 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
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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
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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
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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
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00107471
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| 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 |
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00107471 |
| Other Study ID Numbers: |
ACNS0224 CDR0000417842 ( Other Identifier: Clinical Trials.gov ) COG-ACNS0224 ( Other Identifier: Children's Oncology Group ) |
| First Posted: | April 6, 2005 Key Record Dates |
| Last Update Posted: | December 10, 2013 |
| Last Verified: | December 2013 |
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untreated childhood brain stem glioma |
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Glioma Nervous System Neoplasms Central Nervous System Neoplasms Neoplasms Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms by Site |
Nervous System Diseases Topotecan Lenograstim Adjuvants, Immunologic Immunologic Factors Physiological Effects of Drugs Topoisomerase I Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |