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Clinical Trials (PDQ®)

Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Previously Untreated, High-Risk Medulloblastoma

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIIBiomarker/Laboratory analysis, TreatmentActive3 to 21NCI, OtherACNS0332
NCI-2009-00336, COG-ACNS0332, CDR0000511991, R01CA114567, U10CA098543, U10CA180886, NCT00392327

Trial Description

Summary

This randomized phase III trial studies different chemotherapy and radiation therapy regimens to compare how well they work in treating young patients with newly diagnosed, previously untreated, high-risk medulloblastoma. Drugs used in chemotherapy, such as vincristine sulfate, cisplatin, cyclophosphamide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Isotretinoin may help chemotherapy work better by making tumor cells more sensitive to the drugs. Radiation therapy uses high-energy x-rays to kill tumor cells. Carboplatin may make tumor cells more sensitive to radiation therapy. It is not yet known which chemotherapy and radiation therapy regimen is more effective in treating brain tumors.

Further Study Information

PRIMARY OBJECTIVES:

I. To determine whether carboplatin radiosensitization increases long term event-free survival for high risk medulloblastoma/primitive neuroectodermal tumor (PNET) patients.

II. To determine whether isotretinoin increases long term event-free survival for high risk medulloblastoma/PNET patients.

SECONDARY OBJECTIVES:

I. To compare residual disease response to radiation alone versus radiation plus carboplatin.

II. To identify molecular prognostic indicators suitable for patient stratification in future trials.

III. To evaluate the health-related quality of life (HRQOL) during phases of active treatment specific to treatment modalities.

IV. To describe the neuropsychological functioning of the study population and to evaluate the relationship between neuropsychological status and health related quality of life.

OUTLINE: Patients are randomized to 1 of 4 treatment arms.

ARM I (standard chemoradiotherapy and standard maintenance therapy):

CHEMORADIOTHERAPY: Patients undergo radiation therapy once daily (QD) five days a week for 6 weeks. Patients also receive vincristine sulfate intravenously (IV) over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.

MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim subcutaneously (SC) or IV beginning on day 4 and continuing until blood counts recover (at least 10 days). Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.

ARM II (standard chemoradiotherapy plus carboplatin and standard maintenance therapy):

CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm I. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.

MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm I.

ARM III (standard chemoradiotherapy, standard maintenance therapy plus isotretinoin, and continuation therapy with isotretinoin):

CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm I. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.

MAINTENANCE THERAPY: Patients receive isotretinoin orally (PO) twice daily (BID) on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm I maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy.

CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

ARM IV (standard chemoradiotherapy plus carboplatin, standard maintenance therapy plus isotretinoin, and continuation therapy with isotretinoin):

CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm II. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.

MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm III. Patients then proceed to continuation therapy.

CONTINUATION THERAPY: Patients receive continuation therapy as in Arm III.

After completion of study treatment, patients are followed up periodically for up to 10 years.

Eligibility Criteria

Inclusion Criteria:

  • Newly diagnosed, previously untreated: (1) M0 medulloblastoma with > 1.5 cm^2 residual; (2) M+ medulloblastoma; patients with diffusely anaplastic medulloblastoma are eligible regardless of M-stage or residual tumor
  • As of amendment # 2, enrollment of patients with supratentorial PNET has been discontinued
  • All patients with M4 disease are not eligible
  • A pre-operative magnetic resonance imaging (MRI) scan of the brain with and without contrast is required; NOTE: computed tomography (CT) scans are NOT sufficient for study eligibility
  • Post-operative head MRI scan with and without contrast (preferably within 72 hours post-surgery); for patients who undergo stereotactic biopsy only, either a pre or post-operative MRI is sufficient; for patients with M2 and M3 disease, a post-op MRI is strongly encouraged, but not mandatory
  • Spinal MRI imaging with and without gadolinium is required within 10 days of surgery if done pre-operatively or within 28 days of surgery if done post-operatively; for posterior fossa tumors, pre-operative MRI scans are preferred
  • Lumbar cerebrospinal fluid (CSF) cytology examination must be obtained pre-operatively or within 31 days following surgery; the optimal time for obtaining CSF is prior to surgery or 1-3 weeks following surgery; ventricular CSF (either pre- or post-op) may be used only if a post-operative spinal tap is contraindicated; if a spinal tap is contraindicated and there is no ventricular CSF available, then CSF cytology can be waived for patients with supratentorial tumors or if there is documentation of spinal subarachnoid metastases (M3); patients who are categorized as M1 must have either an intra-operative positive CSF (via lumbar puncture at the end of the procedure) or a positive lumbar CSF obtained > 7 days post-operatively
  • Patients must have a Karnofsky performance level of >= 30 for patients > 16 years of age or a Lansky performance scale of >= 30 for patients =< 16 years of age and life expectancy > 8 weeks
  • No previous chemotherapy or radiation therapy
  • Patients taking Accutane (isotretinoin) for acne must discontinue drug use with this indication prior to enrollment; corticosteroids should not be used during chemotherapy administration as an antiemetic
  • Isotretinoin is contraindicated in patients with parabens allergy and patients with soybean allergy; concurrent use with tetracyclines should be avoided; intake of vitamin A should be limited for the duration of isotretinoin treatment
  • Selected strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (cytochrome P450 3A4) include azole antifungals, such as fluconazole, voriconazole, itraconazole, ketoconazole, and strong inducers include drugs such as rifampin, phenytoin, phenobarbitol, carbamazepine, and St. John's wort; the use of these drugs should be avoided with vincristine (vincristine sulfate)
  • CYP450 3A4 stimulators or inhibitors should be avoided or used with great caution when taking cyclophosphamide; aprepitant should also be used with caution with etoposide or vincristine chemotherapy
  • Cisplatin should be used with caution with nephrotoxic drug; aminoglycoside should be avoided or used with caution during or shortly after cisplatin administration and concomitant use with amphotericin B should probably also be avoided; patients receiving cisplatin and other potentially ototoxic drugs such as aminoglycoside or loop diuretics concomitantly should be closely monitored for signs of ototoxicity
  • Plasma levels of anticonvulsant agents should be monitored and doses adjusted during therapy with cisplatin
  • No other experimental therapy is permitted while on study
  • 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:
  • 0.4 mg/dL (1 month to < 6 months of age)
  • 0.5 mg/dL (6 months to < 1 year of age)
  • 0.6 mg/dL (1 to < 2 years of age)
  • 0.8 mg/dL (2 to < 6 years of age)
  • 1.0 mg/dL (6 to < 10 years of age)
  • 1.2 mg/dL (10 to < 13 years of age)
  • 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
  • 1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age)
  • 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; for patients on anti-seizure medications, SGOT (AST) or SGPT (ALT) must be < 5 x ULN
  • Absolute neutrophil count (ANC) >= 1,000/uL
  • Platelets >= 100,000/uL (untransfused)
  • Hemoglobin >= 8 g/dl (may be transfused)
  • Female patients who are post-menarchal must have a negative pregnancy test; lactating female patients must agree not to breast-feed while on this trial; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Trial Contact Information

Trial Lead Organizations/Sponsors

Children's Oncology Group

National Cancer Institute

James Olson, MD, PhDPrincipal Investigator

Trial Sites

U.S.A.
Alabama
  Birmingham
 Children's Hospital of Alabama at University of Alabama at Birmingham
 Alyssa T Reddy Ph: 205-934-0309
 UAB Comprehensive Cancer Center
 Alyssa T Reddy Ph: 205-934-0309
California
  Long Beach
 Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
 Theodore Zwerdling Ph: 562-933-5437
  Los Angeles
 Children's Hospital Los Angeles
 Leo Mascarenhas Ph: 323-361-4110
 Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
 Fataneh (Fae) Majlessipour Ph: 310-423-8965
  Madera
 Children's Hospital Central California
 Vonda L Crouse Ph: 866-353-5437
  Oakland
 Children's Hospital and Research Center Oakland
 Carla B Golden Ph: 510-450-7600
  Orange
 Children's Hospital of Orange County
 Violet Shen Ph: 714-997-3000
  Palo Alto
 Lucile Packard Children's Hospital at Stanford University Medical Center
 Neyssa M Marina Ph: 650-498-7061
  Email: clinicaltrials@med.stanford.edu
  Sacramento
 University of California Davis Cancer Center
 Jay Michael S Balagtas Ph: 916-734-3089
Connecticut
  Hartford
 Connecticut Children's Medical Center
 Michael S Isakoff Ph: 860-545-9981
  New Haven
 Yale Cancer Center
 Nina S Kadan-Lottick Ph: 203-785-5702
District of Columbia
  Washington
 Children's National Medical Center
 Jeffrey S Dome Ph: 202-884-2549
Florida
  Hollywood
 Joe DiMaggio Children's Hospital
 Iftikhar Hanif Ph: 954-265-2234
  Miami
 University of Miami Sylvester Comprehensive Cancer Center - Miami
 Julio C Barredo Ph: 866-574-5124
  Email: Sylvester@emergingmed.com
  Orlando
 Florida Hospital Cancer Institute at Florida Hospital Orlando
 Fouad M Hajjar Ph: 407-303-5623
  Saint Petersburg
 All Children's Hospital
 Gregory A Hale Ph: 727-767-2423
  Email: HamblinF@allkids.org
  West Palm Beach
 Kaplan Cancer Center at St. Mary's Medical Center
 Narayana Gowda Ph: 888-823-5923
  Email: ctsucontact@westat.com
Georgia
  Atlanta
 AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
 Glen Lew Ph: 404-785-1112
Idaho
  Boise
 Mountain States Tumor Institute at St. Luke's Regional Medical Center
 Eugenia Chang Ph: 800-845-4624
Illinois
  Chicago
 Ann and Robert H. Lurie Children's Hospital of Chicago
 Stewart Goldman Ph: 773-880-4562
 University of Illinois Cancer Center
 Mary L Schmidt Ph: 312-355-3046
  Maywood
 Cardinal Bernardin Cancer Center at Loyola University Medical Center
 Ricarchito B Manera Ph: 708-226-4357
  Oak Lawn
 Keyser Family Cancer Center at Advocate Hope Children's Hospital
 Ammar Hayani Ph: 800-323-8622
  Park Ridge
 Advocate Lutheran General Cancer Care Center
 Jong-Hyo Kwon Ph: 847-384-3621
  Springfield
 Simmons Cooper Cancer Institute
 Gregory P Brandt Ph: 217-545-7929
Indiana
  Indianapolis
 Riley's Children Cancer Center at Riley Hospital for Children
 Robert J Fallon Ph: 317-274-2552
Iowa
  Des Moines
 Blank Children's Hospital
 Wendy L Woods-Swafford Ph: 515-241-6729
Kentucky
  Lexington
 University of Kentucky Chandler Medical Center
 Chainarong Limvarapuss Ph: 707-554-5326
  Louisville
 Kosair Children's Hospital
 Kenneth G Lucas Ph: 866-530-5516
  Email: CTO@hmc.psu.edu
Maine
  Bangor
 CancerCare of Maine at Eastern Maine Medical Center
 Sam W Lew Ph: 401-444-1488
Maryland
  Baltimore
 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
 Kenneth J Cohen Ph: 410-955-8804
  Email: jhcccro@jhmi.edu
Michigan
  Ann Arbor
 C.S. Mott Children's Hospital at University of Michigan Medical Center
 Patricia L Robertson Ph: 800-865-1125
  Detroit
 Van Elslander Cancer Center at St. John Hospital and Medical Center
 Hadi Sawaf Ph: 313-343-3166
 Wayne State University
 Kanta Bhambhani Ph: 313-576-9363
  Kalamazoo
 Bronson Methodist Hospital
 Katharina E Elliott Ph: 800-227-2345
 Western Michigan University School of Medicine Clinics
 Jeffrey S Lobel Ph: 800-227-2345
Minnesota
  Rochester
 Mayo Clinic Cancer Center
 Carola A. S. Arndt Ph: 507-538-7623
Missouri
  Saint Louis
 David C. Pratt Cancer Center at St. John's Mercy
 Bethany G. Sleckman Ph: 913-948-5588
 Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
 Joshua B Rubin Ph: 800-600-3606
  Email: info@siteman.wustl.edu
Nebraska
  Omaha
 Children's Hospital
 Minnie Abromowitch Ph: 402-955-3949
Nevada
  Las Vegas
 CCOP - Nevada Cancer Research Foundation
 Jonathan Bernstein Ph: 702-384-0013
New Hampshire
  Lebanon
 Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
 Sara Chaffee Ph: 800-639-6918
  Email: cancer.research.nurse@dartmouth.edu
New Jersey
  Hackensack
 Hackensack University Medical Center Cancer Center
 Burton E Appel Ph: 201-996-2879
  Morristown
 Carol G. Simon Cancer Center at Morristown Memorial Hospital
 Steven L Halpern Ph: 973-971-5900
  New Brunswick
 Saint Peter's University Hospital
 Stanley Calderwood Ph: 732-745-8600ext6163
  Email: kcovert@saintpetersuh.com
  Paterson
 St. Joseph's Hospital and Medical Center
 Mary A Bonilla Ph: 973-754-2909
  Summit
 Overlook Hospital
 Steven L Halpern Ph: 973-971-5900
New Mexico
  Albuquerque
 University of New Mexico Cancer Center
 Koh B Boayue Ph: 505-272-6972
New York
  Mineola
 Winthrop University Hospital
 Mark E Weinblatt Ph: 866-946-8476
  New York
 Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
 Alice Lee Ph: 212-305-8615
 Memorial Sloan-Kettering Cancer Center
 Peter G Steinherz Ph: 212-639-7202
  Rochester
 James P. Wilmot Cancer Center at University of Rochester Medical Center
 Jeffrey R Andolina Ph: 585-275-5830
  Syracuse
 SUNY Upstate Medical University Hospital
 Karol H Kerr Ph: 315-464-5476
North Carolina
  Chapel Hill
 Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
 Stuart H Gold Ph: 877-668-0683
  Email: cancerclinicaltrials@med.unc.edu
  Winston-Salem
 Wake Forest University Comprehensive Cancer Center
 Sharon M Castellino Ph: 336-713-6771
North Dakota
  Fargo
 Roger Maris Cancer Center at MeritCare Hospital
 Nathan L Kobrinsky Ph: 701-234-6161
Ohio
  Akron
 Akron Children's Hospital
 Steven J Kuerbitz Ph: 330-543-3193
  Cincinnati
 Cincinnati Children's Hospital Medical Center
 John P Perentesis Ph: 513-636-2799
  Cleveland
 Cleveland Clinic Taussig Cancer Center
 Margaret C Thompson Ph: 866-223-8100
 Seidman Cancer Center at University Hospitals/Case Medical Center
 Yousif (Joe) H Matloub Ph: 216-844-5437
  Columbus
 Nationwide Children's Hospital
 Mark A Ranalli Ph: 614-722-2708
  Dayton
 Dayton Children's - Dayton
 Emmett H Broxson Ph: 800-228-4055
  Toledo
 Toledo Hospital
 Jamie L Dargart Ph: 419-824-1842
Oklahoma
  Oklahoma City
 Oklahoma University Cancer Institute
 Rene Y McNall-Knapp Ph: 405-271-4272
  Email: julie-traylor@ouhsc.edu
Oregon
  Portland
 Legacy Emanuel Children's Hospital
 Janice F Olson Ph: 503-413-2560
 Legacy Emanuel Hospital and Health Center and Children's Hospital
 Janice F Olson Ph: 503-413-2560
Pennsylvania
  Bethlehem
 Lehigh Valley Hospital - Muhlenberg
 Philip M Monteleone Ph: 484-884-2201
  Hershey
 Penn State Children's Hospital
 Lisa M McGregor Ph: 717-531-6012
  Philadelphia
 Children's Hospital of Philadelphia
 Michael J Fisher Ph: 215-590-2810
South Carolina
  Charleston
 Hollings Cancer Center at Medical University of South Carolina
 Jacqueline M Kraveka Ph: 843-792-9321
  Columbia
 Palmetto Health South Carolina Cancer Center
 Ronnie W. Neuberg Ph: 803-434-3680
  Greenville
 Cancer Centers of the Carolinas - Faris Road
 Nichole L Bryant Ph: 864-241-6251
South Dakota
  Sioux Falls
 Sanford Cancer Center at Sanford USD Medical Center
 Kayelyn J Wagner Ph: 605-328-1367
Texas
  Austin
 Dell Children's Medical Center of Central Texas
 Sharon K Lockhart Ph: 512-324-8022
  Corpus Christi
 Driscoll Children's Hospital
 M. C Johnson Ph: 361-694-5311
  Houston
 Dan L. Duncan Cancer Center at Baylor College of Medicine
 Karen R Rabin Ph: 713-798-1354
  Email: burton@bcm.edu
  Lubbock
 Covenant Children's Hospital
 Latha Prasannan Ph: 806-725-8000
  Email: jaccresearch@covhs.org
  San Antonio
 Methodist Children's Hospital of South Texas
 Jaime Estrada Ph: 210-575-7000
  Temple
 Scott and White Cancer Institute
 Guy H Grayson Ph: 254-724-5407
Vermont
  Burlington
 Vermont Cancer Center at University of Vermont
 Alan C Homans Ph: 802-656-8990
Virginia
  Falls Church
 Inova Fairfax Hospital
 Marshall A Schorin Ph: 703-208-6650
  Norfolk
 Children's Hospital of The King's Daughters
 Eric J Lowe Ph: 757-668-7243
  Richmond
 Virginia Commonwealth University Massey Cancer Center
 Asadullah Khan Ph: 804-628-1939
  Roanoke
 Carilion Medical Center for Children at Roanoke Community Hospital
 Mandy M Atkinson Ph: 540-981-7376
Washington
  Seattle
 Children's Hospital and Regional Medical Center - Seattle
 Douglas S Hawkins Ph: 866-987-2000
  Spokane
 Providence Cancer Center at Sacred Heart Medical Center
 Judy L Felgenhauer Ph: 800-228-6618
  Email: HopeBeginsHere@providence.org
  Tacoma
 Mary Bridge Children's Hospital and Health Center - Tacoma
 Robert G Irwin Ph: 253-403-3229
West Virginia
  Charleston
 West Virginia University Medical School - Charleston
 Howard M Grodman Ph: 304-388-9944
Wisconsin
  Green Bay
 St. Vincent Hospital Regional Cancer Center
 John R Hill Ph: 920-433-8889
  Marshfield
 Marshfield Clinic - Marshfield Center
 Michael J McManus Ph: 715-389-4457
  Milwaukee
 Midwest Children's Cancer Center at Children's Hospital of Wisconsin
 Michael E Kelly Ph: 414-805-4380
Canada
Ontario
  Hamilton
 McMaster Children's Hospital at Hamilton Health Sciences
 Carol Portwine Ph: 905-521-2100ext74595

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00392327
ClinicalTrials.gov processed this data on September 16, 2014

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.

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