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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
  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: Intervention Model: Single Group Assignment
Masking: None (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 ]
    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 ]
    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.


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 ]
    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.


Enrollment: 26
Study Start Date: December 2013
Primary Completion Date: December 31, 2016 (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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   up to 47 Months   (Child)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02017964


  Hide Study Locations
Locations
United States, Alabama
Children's Hospital of Alabama
Birmingham, Alabama, United States, 35233
United States, California
Southern California Permanente Medical Group
Downey, California, United States, 90242
Loma Linda University Medical Center
Loma Linda, California, United States, 92354
Childrens Hospital of Orange County
Orange, California, United States, 92868
University of California at Davis Cancer Center
Sacramento, California, United States, 95817
United States, Connecticut
Connecticut Children's Medical Center
Hartford, Connecticut, United States, 06106
United States, Delaware
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, District of Columbia
Children's National Medical Center
Washington, D.C., District of Columbia, United States, 20010
United States, Florida
Nemours Children's Clinic-Jacksonville South
Jacksonville, Florida, United States, 32207
Florida Hospital Orlando
Orlando, Florida, United States, 32803
Arnold Palmer Hospital for Children
Orlando, Florida, United States, 32806
Nemours Children's Hospital
Orlando, Florida, United States, 32827
Nemours Children's Clinic - Pensacola
Pensacola, Florida, United States, 32504
All Children's Hospital
Saint Petersburg, Florida, United States, 33701
Saint Joseph Children's Hospital of Tampa
Tampa, Florida, United States, 33607
Saint Mary's Hospital
West Palm Beach, Florida, United States, 33407
United States, Georgia
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States, 30322
United States, Illinois
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States, 60611
Saint Jude Midwest Affiliate
Peoria, Illinois, United States, 61602
United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Iowa
Blank Children's Hospital
Des Moines, Iowa, United States, 50309
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
Kosair Children's Hospital
Louisville, Kentucky, United States, 40202
United States, Louisiana
Children's Hospital New Orleans
New Orleans, Louisiana, United States, 70118
Ochsner Medical Center Jefferson
New Orleans, Louisiana, United States, 70121
United States, Maryland
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21287
United States, Michigan
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, United States, 49503
United States, Minnesota
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, United States, 55455
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Missouri
The Childrens Mercy Hospital
Kansas City, Missouri, United States, 64108
United States, Nebraska
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, United States, 68114
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Morristown Memorial Hospital
Morristown, New Jersey, United States, 07962
UMDNJ - Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States, 08903
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87106
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
State University of New York Upstate Medical University
Syracuse, New York, United States, 13210
Montefiore Medical Center - Moses Campus
The Bronx, New York, United States, 10467-2490
New York Medical College
Valhalla, New York, United States, 10595
United States, Ohio
Children's Hospital Medical Center of Akron
Akron, Ohio, United States, 44308
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, United States, 44106
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Penn State Hershey Children's Hospital
Hershey, Pennsylvania, United States, 17033
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, South Carolina
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, United States, 29605
United States, Texas
Medical City Dallas Hospital
Dallas, Texas, United States, 75230
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
Baylor College of Medicine
Houston, Texas, United States, 77030
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229
United States, Virginia
Childrens Hospital-King's Daughters
Norfolk, Virginia, United States, 23507
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
United States, Wisconsin
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States, 53226
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6008
Canada, British Columbia
British Columbia Children's Hospital
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Nova Scotia
IWK Health Centre
Halifax, Nova Scotia, Canada, B3J 3G9
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, Canada, H3T 1C5
Centre Hospitalier Universitaire de Quebec
Ste-Foy, Quebec, Canada, G1V 4G2
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 ( 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 )
First Submitted: December 13, 2013
First Posted: December 23, 2013
Last Update Posted: May 17, 2017
Last Verified: May 2017

Additional relevant MeSH terms:
Medulloblastoma
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
Methotrexate
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