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Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed, Non-Metastatic Desmoplastic Medulloblastoma

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02017964
First Posted: December 23, 2013
Last Update Posted: May 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
December 13, 2013
December 23, 2013
May 17, 2017
December 2013
December 31, 2016   (Final data collection date for primary outcome measure)
Progression-free survival (PFS) [ Time Frame: From diagnosis to the earliest of disease progression or death from any cause, assessed at 2 years ]
At the time of the final analysis, 95% exact confidence interval estimate of the binomial probability of completing two years of therapy free of failure will be calculated. In addition Kaplan-Meier estimates of PFS and distributions will be provided.
  • PFS [ Time Frame: From diagnosis to the earliest of disease progression or death from any cause, assessed at 2 years ]
    At the time of the final analysis, 95% exact confidence interval estimate of the binomial probability of completing two years of therapy free of failure will be calculated. In addition Kaplan-Meier estimates of PFS and distributions will be provided.
  • Overall survival [ Time Frame: From diagnosis to death from any cause, assessed up to 72 months ]
    Kaplan-Meier estimates of overall survival distributions will be provided.
  • Event-free survival [ Time Frame: Up to 72 months ]
  • Response rates [ Time Frame: At 189 days ]
    Estimates of response rates as well as the associated exact confidence intervals will be reported.
  • Response rates [ Time Frame: At 273 days ]
    Estimates of response rates as well as the associated exact confidence intervals will be reported.
Complete list of historical versions of study NCT02017964 on ClinicalTrials.gov Archive Site
  • Overall Survival [ Time Frame: From diagnosis to death from any cause, assessed up to 72 months ]
    Kaplan-Meier estimates of overall survival distributions will be provided.
  • Event-free survival [ Time Frame: Up to 72 months ]
  • Response [ Time Frame: At 273 days ]
    Estimates of response rates as well as the associated exact confidence intervals will be reported.
Not Provided
  • Feasibility of rapid central pathology screening review defined as success rate of timely central pathology review based on the expectation that at least 95% of the cases will be reviewed within 10 days from receipt of slides [ Time Frame: Up to 10 days ]
    At the end of the trial the feasibility of such a prescreening process will be assessed by reporting various performance statistics including the percentage and the associated confidence interval of cases where the central review was obtained within 10 days from receipt of slides as well as summary statistics of the actual review times.
  • Change in neurocognitive and adaptive functioning assessed using Full Scale IQ score (FSIQ) and General Adaptive Composite score (GAC) [ Time Frame: Baseline to up to 60 months ]
    Changes will be described via paired tests and confidence intervals both for FSIQ and GAC in order to capture any deterioration over time.
  • Feasibility of rapid central pathology screening review defined as success rate of timely central pathology review based on the expectation that at least 95% of the cases will be reviewed within 10 days [ Time Frame: Up to 10 days ]
    At the end of the trial the feasibility of such a prescreening process will be assessed by reporting various performance statistics including the percentage and the associated confidence interval of cases where the central review was obtained within 10 days from receipt of slides as well as summary statistics of the actual review times. Further frequency tables and other descriptive statistics will be provided summarizing the agreement between the site pathologists and the central pathology reviewers as well as among the central pathology reviewers.
  • Molecular profile [ Time Frame: Up to 3 years ]
    Contingency table analysis will be used to examine the association of molecular abnormalities with other categorical characterizations of tumors. If appropriate, associations of continuous markers with specific tumor types will be examined using analysis of variance or the Kruskal-Wallis tests. Significance will be determined using exact, permutation, or resampling methods. Finally associations of such abnormalities with outcome will be explored via Cox models.
  • Change in neurocognitive and adaptive functioning assessed using Full Scale IQ score (FSIQ) and General Adaptive Composite score (GAC) [ Time Frame: Baseline to up to 60 months ]
    Changes will be described via paired tests and confidence intervals both for FSIQ and GAC in order to capture any deterioration over time.
 
Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed, Non-Metastatic Desmoplastic Medulloblastoma
A Phase II Study for the Treatment of Non-metastatic Nodular Desmoplastic Medulloblastoma in Children Less Than 4 Years of Age
This phase II trial studies how well combination chemotherapy works in treating younger patients with newly diagnosed, non-metastatic desmoplastic medulloblastoma. Drugs used in chemotherapy, such as vincristine sulfate, cyclophosphamide, methotrexate, etoposide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PRIMARY OBJECTIVES:

I. Estimate of the progression free survival (PFS) distribution for patients 0-<4 years of age with M0 desmoplastic medulloblastoma (nodular desmoplastic or medulloblastoma with extensive nodularity) treated with the modified HIT SKK regimen (excluding the use of intraventricular methotrexate).

SECONDARY OBJECTIVES:

I. Evaluate the feasibility of a rapid central pathology screening review for treatment allocation according to histology and assess agreement between institutional and central pathology review diagnoses as well as among central pathology review diagnoses.

II. Prospectively evaluate the molecular profile of nodular desmoplastic (ND)/medulloblastoma with extensive nodularity (MBEN) medulloblastoma in young children.

III. Monitor and describe the neurocognitive and adaptive functioning of young children with ND/MBEN medulloblastoma treated on this protocol using the ALTE07C1 protocol.

OUTLINE:

INDUCTION THERAPY: Patients receive vincristine sulfate intravenously (IV) over 1 minute or infused via minibag on days 1, 15, and 29; cyclophosphamide IV over 1 hour on days 1-3; methotrexate IV over 24 hours on days 15 and 29; etoposide IV over 60-120 minutes on days 43-45; and carboplatin IV over 1 hour on days 43-45. Treatment repeats every 63 days for 3 courses in the absence of disease progression or unacceptable toxicity.

CONTINUATION THERAPY: Patients receive vincristine sulfate IV over 1 minute or infused via minibag on day 1, cyclophosphamide IV over 1 hour on days 1-3, etoposide IV over 60-120 minutes on days 21-23, and carboplatin IV over 1 hour on days 21-23. Treatment repeats every 42 days for 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3, 6, 9, 12, 16, 20, 24, 36, 48, 60, and 72 months.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Untreated Childhood Medulloblastoma
  • Drug: Vincristine Sulfate
    Given IV
    Other Names:
    • Kyocristine
    • Oncovin
    • VCR
    • Vincasar
  • Drug: Cyclophosphamide
    Given IV
  • Drug: Methotrexate
    Given IV
  • Drug: Etoposide
    Given IV
    Other Name: Lastet
  • Drug: Carboplatin
    Given IV
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Cognitive Assessment
    Optional ancillary studies
Experimental: Treatment (combination chemotherapy)

INDUCTION THERAPY: Patients receive vincristine sulfate IV over 1 minute or infused via minibag on days 1, 15, and 29; cyclophosphamide IV over 1 hour on days 1-3; methotrexate IV over 24 hours on days 15 and 29; etoposide IV over 60-120 minutes on days 43-45; and carboplatin IV over 1 hour on days 43-45. Treatment repeats every 63 days for 3 courses in the absence of disease progression or unacceptable toxicity.

CONTINUATION THERAPY: Patients receive vincristine sulfate IV over 1 minute or infused via minibag on day 1, cyclophosphamide IV over 1 hour on days 1-3, etoposide IV over 60-120 minutes on days 21-23, and carboplatin IV over 1 hour on days 21-23. Treatment repeats every 42 days for 2 courses in the absence of disease progression or unacceptable toxicity.

Interventions:
  • Drug: Vincristine Sulfate
  • Drug: Cyclophosphamide
  • Drug: Methotrexate
  • Drug: Etoposide
  • Drug: Carboplatin
  • Other: Laboratory Biomarker Analysis
  • Other: Cognitive Assessment
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
26
Not Provided
December 31, 2016   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must be newly diagnosed and have a confirmed histologic diagnosis of nodular desmoplastic (ND) medulloblastoma or medulloblastoma with extensive nodularity (MBEN) from rapid central pathology screening review; please note: patients with Gorlin syndrome are eligible
  • Patient must have negative lumbar cerebrospinal fluid (CSF) cytology (lumbar CSF must be obtained unless medically contraindicated); CSF cytology for staging should be performed no sooner than 14 days post operatively, preferably between day 14 and day 21 to allow for final staging status before enrollment onto the study
  • Patients must have:

    • Pre-operative cranial magnetic resonance imaging (MRI) (recommended with gadolinium) or pre-operative computed tomography (CT) (recommended with contrast)
    • Post-operative cranial MRI with and without gadolinium within 72 hours of surgery
    • Spinal MRI pre-op with and without gadolinium or post-op with and without gadolinium within 72 hours of surgery
  • Patients must be enrolled on study within 31 days of definitive surgical resection at which time tissue is acquired to determine a diagnosis; patients must be enrolled before treatment begins; the date protocol therapy is projected to start must be no later than five (5) calendar days after the date of study enrollment; patients who are started on protocol therapy on a Phase II study prior to study enrollment will be considered ineligible
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Lansky for patients =< 16 years of age
  • Patients must have a life expectancy of >= 8 weeks
  • Patients who are receiving dexamethasone must be on a stable dose for at least 1 week prior to study entry
  • Peripheral absolute neutrophil count (ANC) >= 1000/uL
  • Platelet count >= 100,000/uL (transfusion independent)
  • Hemoglobin >= 10.0 g/dL (may receive red blood cell [RBC] transfusions)
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

    • 1 month to < 6 months: 0.4 mg/dL
    • 6 months to < 1 year: 0.5 mg/dL
    • 1 to < 2 years: 0.6 mg/dL
    • 2 to < 6 years: 0.8 mg/dL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age
  • Central nervous system function defined as:

    • Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
    • Patients must not be in status, coma or assisted ventilation prior to study enrollment

Exclusion Criteria:

  • Patients with metastatic disease by either MRI evaluation (brain and spine) or lumbar CSF cytology are not eligible
  • Patients must not have received any prior tumor-directed therapy other than surgical intervention and corticosteroids
Sexes Eligible for Study: All
up to 47 Months   (Child)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Canada,   United States
 
 
NCT02017964
ACNS1221
NCI-2013-02379 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
COG-ACNS1221 ( Other Identifier: Children's Oncology Group )
ACNS1221 ( Other Identifier: Children's Oncology Group )
ACNS1221 ( Other Identifier: CTEP )
U10CA098543 ( U.S. NIH Grant/Contract )
U10CA180886 ( U.S. NIH Grant/Contract )
Yes
Not Provided
Not Provided
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Lucie Lafay-Cousin, MD Children's Oncology Group
Children's Oncology Group
May 2017

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