Trial record 1 of 1 for:    ACNS0331
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Comparison of Radiation Therapy Regimens in Combination With Chemotherapy in Treating Young Patients With Newly Diagnosed Standard-Risk Medulloblastoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Children's Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00085735
First received: June 14, 2004
Last updated: February 11, 2014
Last verified: February 2014
  Purpose

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as vincristine, cisplatin, lomustine, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy with chemotherapy after surgery may kill any remaining tumor cells. It is not yet known whether standard-dose radiation therapy combined with chemotherapy after surgery is more effective than reduced-dose craniospinal (head and spine) radiation therapy plus either posterior fossa (back of the brain) boost or tumor bed (site of the tumor) boost radiation therapy combined with chemotherapy in treating medulloblastoma.

PURPOSE: This randomized phase III trial is studying standard-dose radiation therapy to see how well it works compared to reduced-dose craniospinal radiation therapy AND posterior fossa boost radiation therapy to see how well it works compared to tumor bed boost radiation therapy when given together with chemotherapy in treating young patients who have undergone surgery for newly diagnosed standard-risk medulloblastoma.


Condition Intervention Phase
Brain Tumor
Central Nervous System Tumor
Drug: cisplatin
Drug: cyclophosphamide
Drug: lomustine
Drug: vincristine sulfate
Radiation: radiation therapy
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 Study Evaluating Limited Target Volume Boost Irradiation and Reduced Dose Craniospinal Radiotherapy (18.00 Gy) and Chemotherapy in Children With Newly Diagnosed Standard Risk Medulloblastoma: A Phase III Double Randomized Trial

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Time to event-free survival (EFS) [ Time Frame: Time from study entry to disease progression, disease recurrence, death from any cause, or occurrence of a second malignant neoplasm, assessed up to 3 years ] [ Designated as safety issue: No ]
    Time-to-event for radiation therapy question will be based on logrank test. Interim monitoring for each study question will be based on the Lan-Demets criterion, with spending function αt. The time point for 100% information is defined as two years after the last patient has enrolled. Information expended will be computed based on the current available follow-up, using the parametric cure model for A9961.


Secondary Outcome Measures:
  • Time to recurrence, progression, or death due to cancer [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Used to compute progression-free survival (PFS) percent. Death from causes that are clearly not associated with tumor recurrence or progression will be censored in this analysis

  • Time to death from any cause [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Used to compute survival (S) percent.

  • Local posterior fossa (LPF) failure [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    LPF failure is defined as tumor recurrence or progression within the tumor bed; i.e., within clinical target volume (CTV)boost for patients randomized to tumor-bed-only (involved field) boost (or within a theoretical CTVboost for patients randomized to standard PF radiation therapy). Recurrent tumors that straddle the boundary of CTVboost will be classified as LPF if more than 50% of the tumor volume is within CTVboost.

  • Non-local posterior fossa (NLPF) failure [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    NLPF failure is defined as tumor outside CTVboost, but within CTVPF. Recurrent tumors that straddle the boundary of CTVboost will be classified as non-local posterior fossa (NLPF) if more than 50% of the tumor volume is outside of CTVboost. Recurrent tumors that straddle the boundary of CTVPF will be classified as LPF if more than 50% of the tumor volume is within CTVPF

  • Non-posterior fossa (NPF) failure [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    NPF is defined as tumor recurrence within the neuroaxis but outside of CTVPF. Recurrent tumors that straddle the boundary of CTVPF will be classified as NPF if more than 50% of the tumor volume is outside of CTVPF.

  • Post-treatment neurocognitive function as measured by neuropsychometric battery [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    The analysis of toxicity and morbidity will compare the rates of adverse consequences of radiation therapy between treatment groups. The power of these comparisons can be demonstrated by reference to a two-sample test of means of normal random variables.

  • Post-treatment hearing loss as measure by audiogram or brainstem auditory evoked response (BAER) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    The analysis of toxicity and morbidity will compare the rates of adverse consequences of radiation therapy between treatment groups. The power of these comparisons can be demonstrated by reference to a two-sample test of means of normal random variables.

  • Post-treatment endocrine function (e.g., growth, sexual maturation, and need for hormone replacement) by laboratory assessment, clinical history, and exam [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    The analysis of toxicity and morbidity will compare the rates of adverse consequences of radiation therapy between treatment groups. The power of these comparisons can be demonstrated by reference to a two-sample test of means of normal random variables.

  • Quality of Life as measured by Pediatric Quality of Life Inventory (PedsQL), Behavior Assessment System for Children (BASC), Behavior Rating Inventory of Executive Function (BRIEF), and Adaptive Behavior Assessment System (ABAS) at 3 years [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Incidence of grade 3 and grade 4 toxicities in any body system as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events v 4.0 [ Time Frame: At baseline, during and after completion of study treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 510
Study Start Date: April 2004
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (reduced craniospinal XRT, XRT tumor bed & Regimen A)
Patients undergo reduced-dose craniospinal radiation therapy with boost. Patients will undergo radiotherapy boost to the tumor bed only. Patients receive oral lomustine and cisplatin IV over 6 hours on day 1 and vincristine sulfate IV on days 1, 8, and 15 of weeks 11, 17, 27, 33, 43, and 49.
Drug: cisplatin
Given IV
Other Names:
  • Cis-diamminedichloroplatinum II
  • CDDP
  • cis-DDP
  • Platinol-AQ
  • NSC #119875
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #26271
Drug: lomustine
Given orally
Other Names:
  • Cyclohexylchloroethylnitrosourea
  • CCNU
  • CeeNU
  • NSC #79037
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Radiation: radiation therapy
Given on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6) at different doses.
Experimental: Arm II (reduced craniospinal XRT, XRT tumor bed & Regimen B)
Patients undergo reduced-dose craniospinal radiation therapy with boost. Smaller volume boost radiation to tumor bed. Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and vincristine sulfate IV on days 1 and 8 of weeks 23, 39, and 55.
Drug: cisplatin
Given IV
Other Names:
  • Cis-diamminedichloroplatinum II
  • CDDP
  • cis-DDP
  • Platinol-AQ
  • NSC #119875
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #26271
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Radiation: radiation therapy
Given on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6) at different doses.
Experimental: Arm III (std craniospinal XRT, XRT tumor bed & Regimen A)
Patients undergo standard-dose craniospinal radiation therapy with boost. Standard volume boost (radiation to the entire posterior fossa. Patients receive oral lomustine and cisplatin IV over 6 hours on day 1 and vincristine sulfate IV on days 1, 8, and 15 of weeks 11, 17, 27, 33, 43, and 49.
Drug: cisplatin
Given IV
Other Names:
  • Cis-diamminedichloroplatinum II
  • CDDP
  • cis-DDP
  • Platinol-AQ
  • NSC #119875
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #26271
Drug: lomustine
Given orally
Other Names:
  • Cyclohexylchloroethylnitrosourea
  • CCNU
  • CeeNU
  • NSC #79037
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Radiation: radiation therapy
Given on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6) at different doses.
Experimental: Arm IV (std craniospinal XRT, XRT tumor bed & Regimen B)
Patients undergo standard-dose craniospinal radiation therapy with boost. Smaller volume boost radiation to tumor bed. Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and vincristine sulfate IV on days 1 and 8 of weeks 23, 39, and 55.
Drug: cisplatin
Given IV
Other Names:
  • Cis-diamminedichloroplatinum II
  • CDDP
  • cis-DDP
  • Platinol-AQ
  • NSC #119875
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #26271
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Radiation: radiation therapy
Given on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6) at different doses.
Experimental: Arm V (reduced craniospinal XRT, XRT fossa & Regimen A)
Patients undergo reduced-dose craniospinal radiation therapy with boost. Standard volume boost (radiation to the entire posterior fossa. Patients receive oral lomustine and cisplatin IV over 6 hours on day 1 and vincristine sulfate IV on days 1, 8, and 15 of weeks 11, 17, 27, 33, 43, and 49.
Drug: cisplatin
Given IV
Other Names:
  • Cis-diamminedichloroplatinum II
  • CDDP
  • cis-DDP
  • Platinol-AQ
  • NSC #119875
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #26271
Drug: lomustine
Given orally
Other Names:
  • Cyclohexylchloroethylnitrosourea
  • CCNU
  • CeeNU
  • NSC #79037
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Radiation: radiation therapy
Given on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6) at different doses.
Experimental: Arm VI (reduced craniospinal XRT, XRT fossa & Regimen B)
Patients undergo reduced-dose craniospinal radiation therapy with boost. Standard volume boost (radiation to the entire posterior fossa. Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and vincristine sulfate IV on days 1 and 8 of weeks 23, 39, and 55.
Drug: cisplatin
Given IV
Other Names:
  • Cis-diamminedichloroplatinum II
  • CDDP
  • cis-DDP
  • Platinol-AQ
  • NSC #119875
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #26271
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Radiation: radiation therapy
Given on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6) at different doses.
Experimental: Arm VII (std craniospinal XRT, XRT fossa & Regimen A)
Patients undergo standard-dose craniospinal radiation therapy with boost. Smaller volume boost radiation to tumor bed. Patients receive oral lomustine and cisplatin IV over 6 hours on day 1 and vincristine sulfate IV on days 1, 8, and 15 of weeks 11, 17, 27, 33, 43, and 49.
Drug: cisplatin
Given IV
Other Names:
  • Cis-diamminedichloroplatinum II
  • CDDP
  • cis-DDP
  • Platinol-AQ
  • NSC #119875
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #26271
Drug: lomustine
Given orally
Other Names:
  • Cyclohexylchloroethylnitrosourea
  • CCNU
  • CeeNU
  • NSC #79037
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Radiation: radiation therapy
Given on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6) at different doses.
Experimental: Arm VIII (std craniospinal XRT, XRT fossa & Regimen B)
Patients undergo standard-dose craniospinal radiation therapy with boost. Standard volume boost (radiation to the entire posterior fossa. Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and vincristine sulfate IV on days 1 and 8 of weeks 23, 39, and 55.
Drug: cisplatin
Given IV
Other Names:
  • Cis-diamminedichloroplatinum II
  • CDDP
  • cis-DDP
  • Platinol-AQ
  • NSC #119875
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #26271
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Radiation: radiation therapy
Given on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6) at different doses.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed medulloblastoma located in the posterior fossa

    • Standard-risk disease
  • Minimal volume, non-disseminated disease, defined by the following:

    • Residual tumor ≤ 1.5 cm^2 confirmed by MRI with contrast imaging within 21 days after surgery
    • No metastatic disease in the head, spine, or cerebrospinal fluid (CSF) confirmed by both of the following:

      • Enhanced MRI of the spine within 5 days before surgery OR within 28 days after surgery
      • Negative cytological examination of CSF after surgery, but before study enrollment
  • Brain stem involvement allowed

PATIENT CHARACTERISTICS:

Age

  • 3 to 21 at diagnosis

Performance status

  • Karnofsky 50-100% (> 16 years of age) OR
  • Lansky 30-100% (≤ 16 years of age)

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count > 1,500/mm^3
  • Platelet count > 100,000/mm^3 (transfusion independent)
  • Hemoglobin > 10 g/dL (transfusions allowed)

Hepatic

  • Bilirubin < 1.5 times upper limit of normal (ULN)
  • AST or ALT < 1.5 times ULN

Renal

  • Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior chemotherapy

Endocrine therapy

  • Prior corticosteroids allowed

Radiotherapy

  • No prior radiotherapy

Surgery

  • See Disease Characteristics
  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: NCT00085735

  Show 184 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Jeff M. Michalski, MD Washington University Siteman Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00085735     History of Changes
Other Study ID Numbers: ACNS0331, COG-ACNS0331, CDR0000365506
Study First Received: June 14, 2004
Last Updated: February 11, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
untreated childhood medulloblastoma

Additional relevant MeSH terms:
Brain Neoplasms
Medulloblastoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neuroectodermal Tumors, Primitive
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Cisplatin
Cyclophosphamide
Lomustine
Vincristine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on July 28, 2014