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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 ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00085735
First received: June 14, 2004
Last updated: August 12, 2014
Last verified: August 2014

June 14, 2004
August 12, 2014
April 2004
July 2016   (final data collection date for primary outcome measure)
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 2 years after the last enrollment ] [ 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 been enrolled.
Not Provided
Complete list of historical versions of study NCT00085735 on ClinicalTrials.gov Archive Site
  • Time to recurrence, progression, or death due to cancer [ Time Frame: 2 years after the last enrollment ] [ Designated as safety issue: No ]
    Used to compute progression-free survival (PFS) rate. 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: 2 years after the last enrollment ] [ Designated as safety issue: No ]
    Used to compute survival (S) rate.
  • Local posterior fossa (LPF) failure [ Time Frame: 2 years after the last enrollment ] [ 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: 2 years after the last enrollment ] [ 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: 2 years after the last enrollment ] [ 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 5 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 10 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 5 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 ]
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Comparison of Radiation Therapy Regimens in Combination With Chemotherapy in Treating Young Patients With Newly Diagnosed Standard-Risk Medulloblastoma
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

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.

OBJECTIVES:

Primary

  • Compare event-free and overall survival of pediatric patients (3 to 7 years of age) with newly diagnosed standard-risk medulloblastoma treated with standard-dose vs reduced-dose craniospinal radiotherapy and posterior fossa boost vs tumor bed boost radiotherapy in combination with chemotherapy comprising vincristine, cisplatin, lomustine, and cyclophosphamide.
  • Compare event-free and overall survival of these patients (8 to 21 years of age) treated with standard-dose craniospinal radiotherapy and posterior fossa boost vs tumor bed boost radiotherapy in combination with this chemotherapy regimen.

Secondary

  • Compare patterns of failure in patients treated with these regimens.
  • Compare the cognitive, auditory, and endocrinologic effects of these regimens in these patients.
  • Compare the audiologic and endocrinologic toxicity from these regimens in these patients.
  • Develop an optimal gene expression medulloblastoma outcome predictor.
  • Assess quality of life and functional status in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients will undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). Patients receive vincristine IV on days 8, 15, 22, 29, 36, and 43 (weeks 1-6) beginning 31 days after surgery.Patients 3 to 7 years of age are randomized to 1 of 2 chemoradiotherapy arms. Patients 8-21 years old are assigned to arm II.

  • Chemoradiotherapy:Patients will undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). Patients receive vincristine IV on days 8, 15, 22, 29, 36, and 43 (weeks 1-6) beginning 31 days after surgery. Patients 3 to 7 years of age are randomized to 1 of 2 radiotherapy arms (arms I and II). Patients 8-21 years old are assigned to arm II.

    • Radiotherapy (first randomization):

      • Arm I: Patients undergo reduced-dose craniospinal radiotherapy with boost.
      • Arm II: Patients undergo standard-dose craniospinal radiotherapy with boost. All patients are then randomized to 1 of 2 chemoradiotherapy arms (arms III and IV).
    • Radiotherapy boost (second randomization):

      • Arm III: Patients will undergo radiotherapy boost to the entire posterior fossa.
      • Arm IV: Patients will undergo radiotherapy boost to the tumor bed only.
  • Maintenance chemotherapy: Beginning 4 weeks after completion of chemoradiotherapy, patients receive 2 different regimens of maintenance chemotherapy for a total of 9 courses. Each course in regimen A is 6 weeks (42 days) in duration. Each course in regimen B is 4 weeks (28 days) in duration.

    • Regimen A (courses 1, 2, 4, 5, 7, and 8): Patients receive oral lomustine and cisplatin IV over 6 hours on day 1 and vincristine IV on days 1, 8, and 15 of weeks 11, 17, 27, 33, 43, and 49.
    • Regimen B (courses 3, 6, and 9): Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and vincristine IV on days 1 and 8 of weeks 23, 39, and 55.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at 3-6 months after completion of radiotherapy and at 3-4 years after study entry. Neurocognitive function may also be assessed.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Brain Tumor
  • Central Nervous System Tumor
  • 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 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.
    Interventions:
    • Drug: cisplatin
    • Drug: cyclophosphamide
    • Drug: lomustine
    • Drug: vincristine sulfate
    • Radiation: radiation therapy
  • 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.
    Interventions:
    • Drug: cisplatin
    • Drug: cyclophosphamide
    • Drug: vincristine sulfate
    • Radiation: radiation therapy
  • 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.
    Interventions:
    • Drug: cisplatin
    • Drug: cyclophosphamide
    • Drug: lomustine
    • Drug: vincristine sulfate
    • Radiation: radiation therapy
  • 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.
    Interventions:
    • Drug: cisplatin
    • Drug: cyclophosphamide
    • Drug: vincristine sulfate
    • Radiation: radiation therapy
  • 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.
    Interventions:
    • Drug: cisplatin
    • Drug: cyclophosphamide
    • Drug: lomustine
    • Drug: vincristine sulfate
    • Radiation: radiation therapy
  • 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.
    Interventions:
    • Drug: cisplatin
    • Drug: cyclophosphamide
    • Drug: vincristine sulfate
    • Radiation: radiation therapy
  • 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.
    Interventions:
    • Drug: cisplatin
    • Drug: cyclophosphamide
    • Drug: lomustine
    • Drug: vincristine sulfate
    • Radiation: radiation therapy
  • 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.
    Interventions:
    • Drug: cisplatin
    • Drug: cyclophosphamide
    • Drug: vincristine sulfate
    • Radiation: radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
549
Not Provided
July 2016   (final data collection date for primary outcome measure)

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
Both
3 Years to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   Netherlands,   New Zealand,   Puerto Rico,   Switzerland
 
NCT00085735
ACNS0331, COG-ACNS0331, CDR0000365506
Yes
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Study Chair: Jeff M. Michalski, MD Washington University Siteman Cancer Center
Children's Oncology Group
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP