Overview

This trial is active, not recruiting.

Condition untreated childhood medulloblastoma
Treatments vincristine sulfate, cyclophosphamide, methotrexate, etoposide, carboplatin, laboratory biomarker analysis, cognitive assessment
Phase phase 2
Sponsor Children's Oncology Group
Collaborator National Cancer Institute (NCI)
Start date December 2013
End date April 2019
Trial size 42 participants
Trial identifier NCT02017964, ACNS1221, COG-ACNS1221, NCI-2013-02379, U10CA098543, U10CA180886

Summary

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.

United States Illinois, New Jersey, and New Mexico
Other Countries Canada

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
vincristine sulfate Kyocristine
Given IV
cyclophosphamide
Given IV
methotrexate
Given IV
etoposide Lastet
Given IV
carboplatin
Given IV
laboratory biomarker analysis
Correlative studies
cognitive assessment
Optional ancillary studies

Primary Outcomes

Measure
Progression-free survival (PFS)
time frame: From diagnosis to the earliest of disease progression or death from any cause, assessed at 2 years

Secondary Outcomes

Measure
Overall Survival
time frame: From diagnosis to death from any cause, assessed up to 72 months
Event-free survival
time frame: Up to 72 months
Response
time frame: At 273 days

Eligibility Criteria

Male or female participants up to 47 months old.

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

Additional Information

Official title A Phase II Study for the Treatment of Non-metastatic Nodular Desmoplastic Medulloblastoma in Children Less Than 4 Years of Age
Principal investigator Lucie Lafay-Cousin, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Children's Oncology Group.
Location data was received from the National Cancer Institute and was last updated in August 2016.