Trial record 2 of 4 for:    medulloblastoma and methotrexate | Open Studies

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by Children's Oncology Group
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT02017964
First received: December 13, 2013
Last updated: July 8, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Untreated Childhood Medulloblastoma
Drug: Vincristine Sulfate
Drug: Cyclophosphamide
Drug: Methotrexate
Drug: Etoposide
Drug: Carboplatin
Other: Laboratory Biomarker Analysis
Other: Cognitive Assessment
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study for the Treatment of Non-metastatic Nodular Desmoplastic Medulloblastoma in Children Less Than 4 Years of Age

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: From diagnosis to the earliest of disease progression or death from any cause, assessed at 2 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: From diagnosis to death from any cause, assessed up to 72 months ] [ Designated as safety issue: No ]
    Kaplan-Meier estimates of overall survival distributions will be provided.

  • Event-free survival [ Time Frame: Up to 72 months ] [ Designated as safety issue: No ]
  • Response [ Time Frame: At 273 days ] [ Designated as safety issue: No ]
    Estimates of response rates as well as the associated exact confidence intervals will be reported.


Other Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Changes will be described via paired tests and confidence intervals both for FSIQ and GAC in order to capture any deterioration over time.


Estimated Enrollment: 42
Study Start Date: December 2013
Estimated Primary Completion Date: April 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 47 Months   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT02017964

  Show 66 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Lucie Lafay-Cousin, MD Children's Oncology Group
  More Information

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT02017964     History of Changes
Other Study ID Numbers: ACNS1221  NCI-2013-02379  COG-ACNS1221  ACNS1221  ACNS1221  U10CA098543  U10CA180886 
Study First Received: December 13, 2013
Last Updated: July 8, 2016
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Medulloblastoma
Methotrexate
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neuroectodermal Tumors, Primitive
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Cyclophosphamide
Etoposide phosphate
Carboplatin
Etoposide
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on July 24, 2016