Combination Chemotherapy, Radiation Therapy, and an Autologous Peripheral Blood Stem Cell Transplant in Treating Young Patients With Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System
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| ClinicalTrials.gov Identifier: NCT00653068 |
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Recruitment Status :
Active, not recruiting
First Posted : April 4, 2008
Results First Posted : February 13, 2017
Last Update Posted : February 28, 2023
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Sponsor:
Children's Oncology Group
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
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Brief Summary:
This phase III trial studies the side effects of combination chemotherapy, 3-dimensional conformal radiation therapy, and an autologous peripheral blood stem cell transplant, and to see how well they work in treating young patients with atypical teratoid/rhabdoid tumor of the central nervous system. Giving high-dose chemotherapy before an autologous peripheral blood stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as G-CSF, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy or radiation therapy.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Childhood Atypical Teratoid/Rhabdoid Tumor | Radiation: 3-Dimensional Conformal Radiation Therapy Procedure: Autologous Hematopoietic Stem Cell Transplantation Drug: Carboplatin Drug: Cisplatin Drug: Cyclophosphamide Drug: Etoposide Biological: Filgrastim Other: Laboratory Biomarker Analysis Drug: Leucovorin Calcium Drug: Methotrexate Drug: Thiotepa Drug: Vincristine Sulfate | Phase 3 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 70 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Treatment of Atypical Teratoid/Rhabdoid Tumors (AT/RT) of the Central Nervous System With Surgery, Intensive Chemotherapy, and 3-D Conformal Radiation |
| Actual Study Start Date : | December 8, 2008 |
| Actual Primary Completion Date : | September 27, 2016 |
| Estimated Study Completion Date : | August 30, 2023 |
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| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers. Within 2-6 weeks after induction therapy or radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. After consolidation therapy, patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks. |
Radiation: 3-Dimensional Conformal Radiation Therapy
Undergo 3D-CRT
Other Names:
Procedure: Autologous Hematopoietic Stem Cell Transplantation Undergo autologous PBSC rescue
Other Names:
Drug: Carboplatin Given IV
Other Names:
Drug: Cisplatin Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Etoposide Given IV
Other Names:
Biological: Filgrastim Given IV or SC
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Leucovorin Calcium Given IV or PO
Other Names:
Drug: Methotrexate Given IV
Other Names:
Drug: Thiotepa Given IV
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm II (chemotherapy, 3D-CRT, autologous PBSC)
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers. Patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks. Within 2-6 weeks after completion of radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. |
Radiation: 3-Dimensional Conformal Radiation Therapy
Undergo 3D-CRT
Other Names:
Procedure: Autologous Hematopoietic Stem Cell Transplantation Undergo autologous PBSC rescue
Other Names:
Drug: Carboplatin Given IV
Other Names:
Drug: Cisplatin Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Etoposide Given IV
Other Names:
Biological: Filgrastim Given IV or SC
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Leucovorin Calcium Given IV or PO
Other Names:
Drug: Methotrexate Given IV
Other Names:
Drug: Thiotepa Given IV
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Primary Outcome Measures :
- Event-free Survival [ Time Frame: Up to 4 years after study enrollment ]Estimated 4-year EFS where EFS is calculated as the time from study enrollment to disease progression, disease relapse, occurrence of a second malignant neoplasm, death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients without an event are censored at last contact.
- Overall Survival (OS) [ Time Frame: Up to 4 years after study enrollment ]Estimated 4-year survival, where survival is calculated as the time from study enrollment to death from any cause or last follow-up alive whichever occurs first. Kaplan-Meier method is used for estimation. Patients alive at last contact are censored.
- Toxic Death [ Time Frame: During and after completion of study treatment up to 1 year after enrollment. ]The number of patients who experience death that is considered to be primarily attributable to complications of treatment.
Secondary Outcome Measures :
- Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy [ Time Frame: During protocol therapy up to 1 year after enrollment. ]Number of Participants with Nonhematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy.
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| Ages Eligible for Study: | up to 21 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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Diagnosis of CNS atypical teratoid/rhabdoid tumor (AT/RT) or tumors that have a mutation of the INI1 gene (even if the tumor does not have the usual histologic characteristics of AT/RT)
- Patients with extra neural metastasis (M4) or renal rhabdoid tumors are not eligible
- Patients with MRI evidence of spinal disease are eligible
- Must have undergone definitive surgery in the past 31 days
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Cranial MRI (with and without gadolinium) must be done pre-operatively
- Post-operatively, cranial MRI (with and without gadolinium) must be done, preferably within 48 hours of surgery or 10-28 days after surgery
- Entire spinal MRI must be obtained either pre-operatively (with gadolinium) or post-operatively (10-28 days after surgery), prior to study enrollment (with and without gadolinium)
- Life expectancy > 8 weeks
- ANC > 1,000/uL
- Platelet count > 100,000/uL (transfusion independent)
- Hemoglobin > 8 g/dL (RBC transfusions allowed)
- Creatinine clearance (minimum of 12-24 hour urine collection) or radioisotope GFR >= 60 mL/min
- Total bilirubin =< 1.5 times upper limit of normal (ULN) for age
- AST and ALT < 2 times ULN for age
- Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 47% by radionuclide angiogram
- No evidence of dyspnea at rest
- Pulse oximetry > 94% on room air
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
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No prior radiotherapy or chemotherapy except for the following:
- Patients enrolled on protocol ACNS0334 whose tumors demonstrate the INI1 gene mutation are eligible to transfer to this study even if they have received one course of induction therapy (these patients must be re-consented to treatment and restaged)
- Prior corticosteroids allowed
Information from the National Library of Medicine
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): NCT00653068
Locations
Show 94 study locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Alyssa Reddy | Children's Oncology Group |
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00653068 |
| Other Study ID Numbers: |
ACNS0333 NCI-2009-00337 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) ACNS0333 09-0058 CDR0000592812 COG-ACNS0333 ACNS0333 ( Other Identifier: Childrens Oncology Group ) ACNS0333 ( Other Identifier: CTEP ) U10CA098543 ( U.S. NIH Grant/Contract ) |
| First Posted: | April 4, 2008 Key Record Dates |
| Results First Posted: | February 13, 2017 |
| Last Update Posted: | February 28, 2023 |
| Last Verified: | February 2023 |
Additional relevant MeSH terms:
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Rhabdoid Tumor Neoplasms, Complex and Mixed Neoplasms by Histologic Type Neoplasms Calcium, Dietary Leucovorin Folic Acid Cyclophosphamide Thiotepa Cisplatin Carboplatin Methotrexate Etoposide Vincristine Etoposide phosphate |
Podophyllotoxin Lenograstim Calcium Levoleucovorin Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Calcium-Regulating Hormones and Agents Bone Density Conservation Agents |