Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00653068
First received: April 3, 2008
Last updated: November 18, 2016
Last verified: November 2016
  Purpose
This phase III trial is studying giving combination chemotherapy together with 3-dimensional conformal radiation therapy and an autologous peripheral blood stem cell transplant to see how well it works 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 Intervention Phase
Childhood Atypical Teratoid/Rhabdoid Tumor
Procedure: autologous hematopoietic stem cell transplantation
Radiation: 3-dimensional conformal radiation therapy
Drug: methotrexate
Drug: leucovorin calcium
Drug: etoposide
Drug: cyclophosphamide
Drug: cisplatin
Biological: filgrastim
Drug: carboplatin
Drug: thiotepa
Drug: vincristine sulfate
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Event-free survival [ Time Frame: Time 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 ]
    For statistical evaluation and data reporting, the study cohort can be regarded as comprising four different strata. Stratum I: Infants (<36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT; Stratum II: Infants with INI1 mutation only based diagnosis (histology is not consistent with AT/RT); Stratum III: Older children (greater than 36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT; and Stratum IV: Older children with INI1 mutation only based diagnosis. A one-sided log-rank test with 5% Type I error rate will be used for stratum I. For patients in strata II through IV, Kaplan-Meier estimates of disease control (event-free survival) and overall survival will be computed and compared to that in stratum I. The comparison with Stratum I will be largely descriptive.

  • Overall survival (S) of patients with histologically and/or molecularly diagnosed AT/RT [ Time Frame: Time to death from any cause, assessed up to 4 years ] [ Designated as safety issue: No ]
    For statistical evaluation and data reporting, the study cohort can be regarded as comprising four different strata: Stratum I: Infants (<36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT; Stratum II: Infants with INI1 mutation only based diagnosis (histology is not consistent with AT/RT); Stratum III: Older children (greater than 36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT; and Stratum IV: Older children with INI1 mutation only based diagnosis. The outcome of stratum 1 patients will be compared with infants identified as having AT/RT on POG 9233 and CCG 9921. For patients in strata II through IV, Kaplan-Meier estimates of disease control (event-free survival) and overall survival will be computed and compared to that in stratum I.

  • Toxic death [ Time Frame: During and after completion of study treatment ] [ Designated as safety issue: Yes ]
    Treatment-related death is defined as death primarily attributable to complications of treatment.


Secondary Outcome Measures:
  • Overall toxicities as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: During and after completion of study treatment ] [ Designated as safety issue: Yes ]
    The occurrence of grade 4 ototoxicity, electrolytic wasting (acidosis), hemorrhagic cystitis, non-hematologic toxicity, or gastrointestinal/mucositis toxicity (defined as mucositis toxicity associated with life-threatening consequences).


Enrollment: 70
Study Start Date: December 2008
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment

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.

Consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses (C) and 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks (R), the order of which depends on patient age, in the absence of disease progression or unacceptable toxicity.

Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous PBSC rescue
Radiation: 3-dimensional conformal radiation therapy
Undergo 3D-CRT
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: leucovorin calcium
Given IV or orally
Other Names:
  • CF
  • CFR
  • LV
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Biological: filgrastim
Given IV or SC
Other Names:
  • G-CSF
  • Neupogen
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: thiotepa
Given IV
Other Names:
  • Oncotiotepa
  • STEPA
  • TESPA
  • Tespamin
  • TSPA
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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 10-28days 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/μL
  • Platelet count > 100,000/μL (transfusion independent)
  • Hemoglobin > 8 g/dL (RBC transfusions allowed)
  • Creatinine clearance (minimum of 12-24 hour urine collection) or radioisotope GFR ≥ 60mL/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
  • 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
  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: NCT00653068

  Show 83 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Alyssa Reddy, MD Children's Oncology Group
  More Information

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00653068     History of Changes
Other Study ID Numbers: ACNS0333  NCI-2009-00337  COG-ACNS0333  ACNS0333  ACNS0333  U10CA098543 
Study First Received: April 3, 2008
Last Updated: November 18, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Rhabdoid Tumor
Central Nervous System Neoplasms
Neoplasms, Complex and Mixed
Neoplasms by Histologic Type
Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Cyclophosphamide
Methotrexate
Thiotepa
Carboplatin
Etoposide
Vincristine
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
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Tubulin Modulators
Antimitotic Agents

ClinicalTrials.gov processed this record on December 08, 2016