Comparison of Radiation Therapy Regimens in Combination With Chemotherapy in Treating Young Patients With Newly Diagnosed Standard-Risk Medulloblastoma

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IIISupportive care, Treatment3 to 21 at diagnosisACNS0331
NCI-2009-00335, CDR0000365506, COG-ACNS0331, NCT00085735

Trial Description

Summary

This randomized phase III trial is studying standard-dose radiation therapy to see how well it works compared to reduced-dose craniospinal radiation therapy AND posterior fossa boost radiation therapy to see how well it works compared to tumor bed boost radiation therapy when given together with chemotherapy in treating young patients who have undergone surgery for newly diagnosed standard-risk medulloblastoma. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as vincristine, cisplatin, lomustine, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy with chemotherapy after surgery may kill any remaining tumor cells. It is not yet known whether standard-dose radiation therapy combined with chemotherapy after surgery is more effective than reduced-dose craniospinal (head and spine) radiation therapy plus either posterior fossa (back of the brain) boost or tumor bed (site of the tumor) boost radiation therapy combined with chemotherapy in treating medulloblastoma.

Further Study Information

PRIMARY OBJECTIVES:

I. Compare event-free and overall survival of pediatric patients (3 to 7 years of age) with newly diagnosed standard-risk medulloblastoma treated with standard-dose vs reduced-dose craniospinal radiotherapy and posterior fossa boost vs tumor bed boost radiotherapy in combination with chemotherapy comprising vincristine, cisplatin, lomustine, and cyclophosphamide.

II. Compare event-free and overall survival of these patients (8 to 21 years of age) treated with standard-dose craniospinal radiotherapy and posterior fossa boost vs tumor bed boost radiotherapy in combination with this chemotherapy regimen.

SECONDARY OBJECTIVES:

I. Compare patterns of failure in patients treated with these regimens.

II. Compare the cognitive, auditory, and endocrinologic effects of these regimens in these patients.

III. Compare the audiologic and endocrinologic toxicity from these regimens in these patients.

IV. Develop an optimal gene expression medulloblastoma outcome predictor.

V. Assess quality of life and functional status in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients will undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). Patients receive vincristine IV on days 8, 15, 22, 29, 36, and 43 (weeks 1-6) beginning 31 days after surgery. Patients 3 to 7 years of age are randomized to 1 of 2 chemoradiotherapy arms. Patients 8-21 years old are assigned to arm II.

CHEMORADIOTHERAPY: Patients will undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). Patients receive vincristine IV on days 8, 15, 22, 29, 36, and 43 (weeks 1-6) beginning 31 days after surgery. Patients 3 to 7 years of age are randomized to 1 of 2 radiotherapy arms (arms I and II). Patients 8-21 years old are assigned to arm II. Radiotherapy (first randomization):

ARM I: Patients undergo reduced-dose craniospinal radiotherapy with boost.

ARM II: Patients undergo standard-dose craniospinal radiotherapy with boost.

All patients are then randomized to 1 of 2 chemoradiotherapy arms (arms III and IV). Radiotherapy boost (second randomization):

ARM III: Patients will undergo radiotherapy boost to the entire posterior fossa.

Arm IV: Patients will undergo radiotherapy boost to the tumor bed only.

MAINTENANCE CHEMOTHERAPY: Beginning 4 weeks after completion of chemoradiotherapy, patients receive 2 different regimens of maintenance chemotherapy for a total of 9 courses. Each course in regimen A is 6 weeks (42 days) in duration. Each course in regimen B is 4 weeks (28 days) in duration.

REGIMEN A (courses 1, 2, 4, 5, 7, and 8): Patients receive oral lomustine and cisplatin IV over 6 hours on day 1 and vincristine IV on days 1, 8, and 15 of weeks 11, 17, 27, 33, 43, and 49.

REGIMEN B (courses 3, 6, and 9): Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and vincristine IV on days 1 and 8 of weeks 23, 39, and 55.

Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at 3-6 months after completion of radiotherapy and at 3-4 years after study entry. Neurocognitive function may also be assessed.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

Eligibility Criteria

Inclusion Criteria:

Brain stem involvement allowed

Performance status - Karnofsky 50-100% (> 16 years of age)

Performance status - Lansky 30-100% (≤ 16 years of age)

Absolute neutrophil count > 1,500/mm^3

Platelet count > 100,000/mm^3 (transfusion independent)

Hemoglobin > 10 g/dL (transfusions allowed)

Bilirubin < 1.5 times upper limit of normal (ULN)

Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min

Not pregnant or nursing

Negative pregnancy test

Fertile patients must use effective contraception

No prior chemotherapy

Prior corticosteroids allowed

No prior radiotherapy

Minimal volume, non-disseminated disease, defined by the following:

Residual tumor ≤ 1.5 cm^2 confirmed by MRI with contrast imaging within 21 days after surgery

No metastatic disease in the head, spine, or cerebrospinal fluid (CSF) confirmed by both of the following:

  • Enhanced MRI of the spine within 5 days before surgery OR within 28 days after surgery
  • Negative cytological examination of CSF after surgery, but before study enrollment

AST or ALT < 1.5 times ULN

Histologically confirmed medulloblastoma located in the posterior fossa

Standard-risk disease

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Children's Oncology Group

  • National Cancer Institute
Jeff M. Michalski, Principal Investigator

Trial Sites

U.S.A.

California
Sacramento

Sutter General Hospital

Jeff M. Michalski

Jeff M. Michalski
Principal Investigator

Santa Barbara

Santa Barbara Cottage Hospital

Daniel J. Greenfield
Ph: 805-682-7300

Daniel J. Greenfield
Principal Investigator

District of Columbia
Washington

MedStar Georgetown University Hospital

Aziza Tahir Shad
Ph: 202-444-0381

Aziza Tahir Shad
Principal Investigator

Florida
West Palm Beach

Saint Mary's Hospital

Narayana Gowda
Ph: 888-823-5923
Email: ctsucontact@westat.com

Narayana Gowda
Principal Investigator

Maryland
Baltimore

University of Maryland/Greenebaum Cancer Center

Jeff M. Michalski

Jeff M. Michalski
Principal Investigator

Michigan
Detroit

Wayne State University/Karmanos Cancer Institute

Jeff M. Michalski

Jeff M. Michalski
Principal Investigator

Kalamazoo

Kalamazoo Center for Medical Studies

Jeffrey S. Lobel
Ph: 800-227-2345

Jeffrey S. Lobel
Principal Investigator

Minnesota
Saint Paul

Children's Hospital and Clinic-Saint Paul

Jeff M. Michalski

Jeff M. Michalski
Principal Investigator

New Jersey
Summit

Overlook Hospital

Steven Lon Halpern
Ph: 973-971-5900

Steven Lon Halpern
Principal Investigator

New Mexico
Albuquerque

University of New Mexico

Jeff M. Michalski

Jeff M. Michalski
Principal Investigator

North Carolina
Durham

Duke University Medical Center

Susan G. Kreissman
Ph: 888-275-3853

Susan G. Kreissman
Principal Investigator

Greenville

East Carolina University

Mauro Grossi
Ph: 252-744-2161

Mauro Grossi
Principal Investigator

Oregon
Portland

Legacy Emanuel Hospital and Health Center

Janice Faye Olson
Ph: 503-413-2560

Janice Faye Olson
Principal Investigator

South Carolina
Greenville

Greenville Cancer Treatment Center

Cary E. Stroud
Ph: 864-241-6251

Cary E. Stroud
Principal Investigator

Canada

Ontario
Hamilton

Chedoke Hospital at Hamilton Health Sciences

Carol Portwine
Ph: 905-521-2100ext74595

Carol Portwine
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00085735

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.