High-Dose Chemotherapy Plus Autologous Stem Cell Transplantation Compared With Intermediate-Dose Chemotherapy Plus Autologous Stem Cell Transplantation With or Without Isotretinoin in Treating Young Patients With Recurrent High-Grade Gliomas
This study has been completed.
Sponsor:
Children's Oncology Group
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00078988
First received: March 8, 2004
Last updated: March 7, 2013
Last verified: March 2013
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Purpose
RATIONALE: Drugs used in chemotherapy, such as carboplatin, thiotepa, and etoposide, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Isotretinoin may be effective in preventing recurrence of glioma. It is not yet known which regimen of chemotherapy plus autologous stem cell transplantation with or without isotretinoin is more effective in treating recurrent high-grade glioma.
PURPOSE: This randomized phase III trial is studying high-dose chemotherapy or intermediate-dose chemotherapy followed by autologous stem cell transplantation to see how well it works compared to high-dose chemotherapy or intermediate-dose chemotherapy followed by autologous stem cell transplantation and isotretinoin in treating young patients with recurrent high-grade glioma.
| Condition | Intervention | Phase |
|---|---|---|
|
Brain Tumor Central Nervous System Tumor |
Biological: filgrastim Drug: carboplatin Drug: etoposide Drug: isotretinoin Drug: thiotepa Procedure: autologous bone marrow transplantation Procedure: peripheral blood stem cell transplantation |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase III Randomized Trial for the Treatment of Pediatric High Grade Gliomas at First Recurrence With a Single High Dose Chemotherapy and Autologous Stem Cell Transplant Versus Three Courses of Intermediate Dose Chemotherapy With Peripheral Blood Stem Cell (PBSC) Support |
Resource links provided by NLM:
Drug Information available for:
Thiotepa
Tretinoin
Isotretinoin
Etoposide
Carboplatin
Etoposide phosphate
Filgrastim
Lenograstim
Granulocyte colony-stimulating factor
U.S. FDA Resources
Further study details as provided by Children's Oncology Group:
Primary Outcome Measures:
- Event-free survival [ Time Frame: om study entry to disease progression, disease relapse, occurrence of a second malignant neoplasm, or death from any cause. assessed up to 4 years ] [ Designated as safety issue: No ]The primary endpoint for the evaluation of treatment efficacy will be event-free survival (EFS)
- Toxic death attributable to complications of treatment in the absence of tumor progression as assessed by NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: Up to 4 years after completion of study treatment ] [ Designated as safety issue: Yes ]Toxic death will be monitored separately in each of the two chemotherapy groups
Secondary Outcome Measures:
- Overall survival (OS) [ Time Frame: ondary e ndpoints include overall survival (OS), which is defined as the time from study entry to death from any cause assessed up to 4 years ] [ Designated as safety issue: No ]Secondary endpoints include overall survival (OS), which is defined as the time from study entry to death from any cause, assessed up to 4 years
| Enrollment: | 1 |
| Study Start Date: | October 2004 |
| Study Completion Date: | September 2006 |
| Primary Completion Date: | September 2006 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I (high-dose chemotherapy and ASCR)
Patients receive high-dose chemotherapy comprising carboplatin IV over 4 hours on days -8 to -6; thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3; and filgrastim (G-CSF) IV or SC once daily beginning on day 1 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 0.
|
Biological: filgrastim
Given IV
Other Names:
Drug: carboplatin
Given IV
Other Names:
Drug: etoposide
Given IV
Other Names:
Drug: isotretinoin
Given IV
Other Names:
Drug: thiotepa
Given IV
Other Names:
Procedure: autologous bone marrow transplantation
Peripheral blood stem cells or bone marrow will be reinfused about 72 hours following completion of the last dose of chemotherapy (Day 0)
Other Name: Stem Cell Reinfusion
Procedure: peripheral blood stem cell transplantation
Filgrastim is to be given daily in the afternoon for 4 days prior to the first harvest and continued until the completion of the daily harvests. The daily PBSC harvesting should be started prior to the fifth dose of filgrastim.
Other Name: Peripheral Stem Cell Collection
|
|
Experimental: Arm II (intermediate-dose chemotherapy and ASCR)
Patients receive intermediate-dose chemotherapy comprising carboplatin IV over 4 hours and thiotepa IV over 3 hours on days 1-2 and G-CSF IV or SC once daily beginning on day 4 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 3. Treatment repeats every 28 days for a total of 3 courses.
|
Biological: filgrastim
Given IV
Other Names:
Drug: carboplatin
Given IV
Other Names:
Drug: thiotepa
Given IV
Other Names:
Procedure: autologous bone marrow transplantation
Peripheral blood stem cells or bone marrow will be reinfused about 72 hours following completion of the last dose of chemotherapy (Day 0)
Other Name: Stem Cell Reinfusion
Procedure: peripheral blood stem cell transplantation
Filgrastim is to be given daily in the afternoon for 4 days prior to the first harvest and continued until the completion of the daily harvests. The daily PBSC harvesting should be started prior to the fifth dose of filgrastim.
Other Name: Peripheral Stem Cell Collection
|
|
Experimental: Arm III (isotretinoin)
Patients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for a total of 6 courses.
|
Drug: isotretinoin
Given IV
Other Names:
|
|
No Intervention: Arm IV (no isotretinoin)
Patients do not receive maintenance therapy.
|
Detailed Description:
OBJECTIVES:
- Compare the event-free survival and overall survival of pediatric patients with recurrent high-grade gliomas treated with a single course of high-dose carboplatin, etoposide, and thiotepa and autologous stem cell transplantation vs multiple courses of intermediate-dose carboplatin and thiotepa and autologous stem cell transplantation with or without isotretinoin.
- Compare the number of hospital days and time to engraftment in patients treated with these regimens.
- Compare the toxic death rate in patients treated with these regimens.
- Compare the tolerability of isotretinoin in patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to pathologic diagnosis (glioblastoma multiforme vs anaplastic astrocytoma vs other high-grade glioma).
Chemotherapy and autologous stem cell reinfusion (ASCR): Patients are randomized to 1 of 2 treatment arms.
- Arm I (high-dose chemotherapy and ASCR): Patients receive high-dose chemotherapy comprising carboplatin IV over 4 hours on days -8 to -6; thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3; and filgrastim (G-CSF) IV or subcutaneously (SC) once daily beginning on day 1 and continuing until blood counts recover. Autologous peripheral blood stem cells (PBSC) or bone marrow are reinfused on day 0.
- Arm II (intermediate-dose chemotherapy and ASCR): Patients receive intermediate-dose chemotherapy comprising carboplatin IV over 4 hours and thiotepa IV over 3 hours on days 1-2 and G-CSF IV or SC once daily beginning on day 4 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 3. Treatment repeats every 28 days for a total of 3 courses.
Maintenance therapy: After recovery from chemotherapy (approximately day 30 post-transplantation), all patients are further randomized to 1 of 2 maintenance arms.
- Arm I: Patients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for a total of 6 courses.
- Arm II: Patients do not receive maintenance therapy. In all arms, treatment continues in the absence of disease progression.
Patients are followed every 3 months for 1 year, every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 80-150 patients (40-75 per treatment arm) will be accrued for this study within 5 years.
Eligibility| Ages Eligible for Study: | up to 20 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed diagnosis of 1 of the following high-grade gliomas:
- Glioblastoma multiforme
- Anaplastic astrocytoma
- Gliosarcoma
- Disease in first relapse
- No primary brainstem or spinal cord gliomas
- No secondary glioblastomas arising after prior treatment for a non-glial tumor
- Prior local radiotherapy of 5,000-6,000 cGy required
- Less than 1.5 cm of residual gadolinium-enhancing tumor in maximal cross-sectional diameter by MRI
- No metastatic tumor by spinal MRI
PATIENT CHARACTERISTICS:
Age
- Under 21 at diagnosis
Performance status
- Lansky 50-100% OR
- Karnofsky 50-100%
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count ≥ 500/mm^3
- Platelet count ≥ 100,000/mm^3 (transfusion independent)
Hepatic
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST or ALT < 2.5 times ULN
Renal
- Glomerular filtration rate ≥ 60 mL/min AND/OR
- Creatinine clearance ≥ 60 mL/min
Cardiovascular
- Shortening fraction ≥ 27% by echocardiogram OR
- Ejection fraction ≥ 50% by MUGA
Pulmonary
- No dyspnea at rest
- No exercise intolerance
- Pulse oximetry > 94%
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- More than 4 weeks since prior chemotherapy
- No prior thiotepa
- No prior myeloablative chemotherapy
Endocrine therapy
- No concurrent corticosteroids
Radiotherapy
- See Disease Characteristics
- More than 8 weeks since prior radiotherapy
- No prior craniospinal radiotherapy
Surgery
- Not specified
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00078988
Show 59 Study Locations
Show 59 Study LocationsSponsors and Collaborators
Children's Oncology Group
Investigators
| Study Chair: | Ziad Khatib, MD | Miami Children's Hospital |
| Study Chair: | Sharon L. Gardner, MD | New York University School of Medicine |
More Information
Additional Information:
No publications provided
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00078988 History of Changes |
| Other Study ID Numbers: | ACNS0231, COG-ACNS0231, CDR0000353207, NCI-2012-02578, U10CA098543 |
| Study First Received: | March 8, 2004 |
| Last Updated: | March 7, 2013 |
| Health Authority: | United States: Federal Government |
Keywords provided by Children's Oncology Group:
|
childhood high-grade cerebral astrocytoma recurrent childhood cerebellar astrocytoma recurrent childhood cerebral astrocytoma |
Additional relevant MeSH terms:
|
Brain Neoplasms Nervous System Neoplasms Central Nervous System Neoplasms Neoplasms by Site Neoplasms Brain Diseases Central Nervous System Diseases Nervous System Diseases Etoposide Etoposide phosphate Tretinoin Thiotepa Carboplatin Isotretinoin Lenograstim |
Antineoplastic Agents, Phytogenic Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Dermatologic Agents Keratolytic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Myeloablative Agonists Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Adjuvants, Immunologic |
ClinicalTrials.gov processed this record on May 19, 2013