A Study of Treatment for Medulloblastoma Using Sodium Thiosulfate to Reduce Hearing Loss
Start Date
2/20/2023
Completion Date
12/31/2029
Summary
This phase III trial tests two hypotheses in patients with low-risk and average-risk medulloblastoma. Medulloblastoma is a type of cancer that occurs in the back of the brain. The term, risk, refers to the chance of the cancer coming back after treatment. Subjects with low-risk medulloblastoma typically have a lower chance of the cancer coming back than subjects with average-risk medulloblastoma. Although treatment for newly diagnosed average-risk and low-risk medulloblastoma is generally effective at treating the cancer, there are still concerns about the side effects of such treatment. Side effects or unintended health conditions that arise due to treatment include learning difficulties, hearing loss or other issues in performing daily activities. Standard therapy for newly diagnosed average-risk or low-risk medulloblastoma includes surgery, radiation therapy, and chemotherapy (including cisplatin). Cisplatin may cause hearing loss as a side effect. In the average-risk medulloblastoma patients, this trial tests whether the addition of sodium thiosulfate (STS) to standard of care chemotherapy and radiation therapy reduces hearing loss. Previous studies with STS have shown that it may help reduce or prevent hearing loss caused by cisplatin. In the low-risk medulloblastoma patients, the study tests whether a less intense therapy (reduced radiation) can provide the same benefits as the more intense therapy. The less intense therapy may cause fewer side effects. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. The overall goals of this study are to see if giving STS along with standard treatment (radiation therapy and chemotherapy) will reduce hearing loss in medulloblastoma patients and to compare the overall outcome of patients with medulloblastoma treated with STS to patients treated without STS on a previous study in order to make sure that survival and recurrence of tumor is not worsened.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the efficacy of sodium thiosulfate (STS) infusion administered during cisplatin-containing chemotherapy cycles (compared to a historical cohort selected from ACNS0331 which received chemotherapy without STS) in reducing hearing loss in children with newly-diagnosed average-risk medulloblastoma. II. To estimate and monitor event-free survival (EFS) in this study against a carefully selected cohort from ACNS0331 to guard against loss of efficacy due to STS. SECONDARY OBJECTIVES: I. To estimate and monitor overall survival (OS) in this study against a carefully selected control cohort from ACNS0331. II. To estimate the incidence of ototoxicity-related cisplatin dose modifications in the average-risk cohort. III. To estimate the incidence of cisplatin-related nephrotoxicity in both the average-risk and low-risk cohorts. IV. To evaluate full scale intelligence neurocognitive outcomes and trajectories of patients with average-risk medulloblastoma treated with STS compared to the control cohort from ACNS0331. V. To evaluate quality of life and psychosocial outcomes and trajectories of patients with average-risk medulloblastoma treated with STS compared to published norms. VI. To estimate and monitor EFS, OS, and patterns of recurrence in patients with low-risk features treated using a reduced craniospinal radiation approach. VII. To evaluate the trajectory of hearing loss in medulloblastoma patients treated with STS. VIII. To evaluate household material hardship as a social determinant of neurocognitive, quality of life, and psychosocial outcomes in patients with average-risk and low risk medulloblastoma. EXPLORATORY OBJECTIVES: I. To obtain paired blood and tumor tissue to be banked for future biology studies involving comprehensive molecular analysis, including but not limited to whole exome sequencing, ribonucleic acid (RNA) sequencing, and methylation. II. To bank blood and cerebrospinal fluid for future studies. III. To evaluate attention, processing speed, memory, and executive function neurocognitive outcomes and trajectories, as well as hearing-related quality of life outcomes and trajectories, of patients with average-risk medulloblastoma treated with STS. IV. To evaluate neurocognitive, quality of life, and psychosocial outcomes of patients with low-risk features treated using a reduced craniospinal radiation approach. OUTLINE: CHEMORADIOTHERAPY: Patients undergo radiation therapy 5 days per week for 6 weeks (weeks 1-6) and receive vincristine intravenously (IV) once weekly on weeks 2-7 in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Beginning 4 weeks after chemoradiotherapy, patients receive lomustine orally (PO) on day 1 of cycles 1, 2, 4, 5, 7, and 8, cisplatin IV over 6 hours on day 1 of cycles 1, 2, 4, 5, 7, and 8, sodium thiosulfate IV over 15 minutes on day 1 of cycles 1, 2, 4, 5, 7, and 8, and cyclophosphamide IV over 30-60 minutes on days 1 and 2 of cycles 3, 6, and 9. Patients also receive vincristine IV on days 1, 8, and 15 of cycles 1, 2, 4, 5, 7, and 8, and on days 1 and 8 of cycles 3, 6, and 9. Treatment repeats every 6 weeks (cycles 1, 2, 4, 5, 7 and 8) or every 4 weeks (cycles 3, 6, and 9) for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo magnetic resonance imaging (MRI) and collection of cerebrospinal fluid (CSF) throughout the study. Patients may also optionally undergo blood sample collection throughout the study. After completion of study treatment, patients are followed up every 3 months for years 1-2, every 6 months for years 3-4, and then annually for years 5-10.
Eligibility Criteria
Age Range: 4 years to 21 years
Interventions
Audiometric Test
Auditory Brainstem Response
Biospecimen Collection
Cisplatin
Cyclophosphamide
Lomustine
Magnetic Resonance Imaging
Quality-of-Life Assessment
Radiation Therapy
Sodium Thiosulfate
Survey Administration
Vincristine
Conditions
Locations
Children's Hospital of Alabama
Birmingham, Alabama 35233
United States
USA Health Strada Patient Care Center
Mobile, Alabama 36604
United States
Phoenix Childrens Hospital
Phoenix, Arizona 85016
United States
Arkansas Children's Hospital
Little Rock, Arkansas 72202-3591
United States
Loma Linda University Medical Center
Loma Linda, California 92354
United States
Miller Children's and Women's Hospital Long Beach
Long Beach, California 90806
United States
Children's Hospital Los Angeles
Los Angeles, California 90027
United States
Valley Children's Hospital
Madera, California 93636
United States
Kaiser Permanente-Oakland
Oakland, California 94611
United States
Children's Hospital of Orange County
Orange, California 92868
United States
University of California Davis Comprehensive Cancer Center
Sacramento, California 95817
United States
Rady Children's Hospital - San Diego
San Diego, California 92123
United States
UCSF Medical Center-Mission Bay
San Francisco, California 94158
United States
Children's Hospital Colorado
Aurora, Colorado 80045
United States
Connecticut Children's Medical Center
Hartford, Connecticut 06106
United States
Yale University
New Haven, Connecticut 06520
United States
Alfred I duPont Hospital for Children
Wilmington, Delaware 19803
United States
Children's National Medical Center
Washington D.C., District of Columbia 20010
United States
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida 33908
United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida 33021
United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida 32207
United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida 33136
United States
Nicklaus Children's Hospital
Miami, Florida 33155
United States
Arnold Palmer Hospital for Children
Orlando, Florida 32806
United States
Nemours Children's Hospital
Orlando, Florida 32827
United States
Nemours Children's Clinic - Pensacola
Pensacola, Florida 32504
United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida 33607
United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia 30329
United States
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii 96826
United States
University of Illinois
Chicago, Illinois 60612
United States
OSF Children's Hospital of Illinois
Peoria, Illinois 61637
United States
Southern Illinois University School of Medicine
Springfield, Illinois 62702
United States
Riley Hospital for Children
Indianapolis, Indiana 46202
United States
Blank Children's Hospital
Des Moines, Iowa 50309
United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa 52242
United States
Norton Children's Hospital
Louisville, Kentucky 40202
United States
Children's Hospital New Orleans
New Orleans, Louisiana 70118
United States
Sinai Hospital of Baltimore
Baltimore, Maryland 21215
United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland 21287
United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts 02114
United States
Dana-Farber Cancer Institute
Boston, Massachusetts 02215
United States
C S Mott Children's Hospital
Ann Arbor, Michigan 48109
United States
Children's Hospital of Michigan
Detroit, Michigan 48201
United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan 49503
United States
Corewell Health Children's
Royal Oak, Michigan 48073
United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota 55404
United States
Mayo Clinic in Rochester
Rochester, Minnesota 55905
United States
University of Mississippi Medical Center
Jackson, Mississippi 39216
United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri 64108
United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri 63104
United States
Washington University School of Medicine
St Louis, Missouri 63110
United States
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska 68114
United States
University of Nebraska Medical Center
Omaha, Nebraska 68198
United States
Saint Peter's University Hospital
New Brunswick, New Jersey 08901
United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey 08903
United States
Newark Beth Israel Medical Center
Newark, New Jersey 07112
United States
Saint Joseph's Regional Medical Center
Paterson, New Jersey 07503
United States
Albany Medical Center
Albany, New York 12208
United States
Roswell Park Cancer Institute
Buffalo, New York 14263
United States
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York 11040
United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York 10016
United States
Mount Sinai Hospital
New York, New York 10029
United States
Stony Brook University Medical Center
Stony Brook, New York 11794
United States
State University of New York Upstate Medical University
Syracuse, New York 13210
United States
Montefiore Medical Center - Moses Campus
The Bronx, New York 10467
United States
New York Medical College
Valhalla, New York 10595
United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina 27599
United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina 28203
United States
East Carolina University
Greenville, North Carolina 27834
United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina 27157
United States
Sanford Broadway Medical Center
Fargo, North Dakota 58122
United States
Children's Hospital Medical Center of Akron
Akron, Ohio 44308
United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio 45229
United States
Rainbow Babies and Childrens Hospital
Cleveland, Ohio 44106
United States
Nationwide Children's Hospital
Columbus, Ohio 43205
United States
Dayton Children's Hospital
Dayton, Ohio 45404
United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio 43606
United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
United States
Legacy Emanuel Children's Hospital
Portland, Oregon 97227
United States
Oregon Health and Science University
Portland, Oregon 97239
United States
Geisinger Medical Center
Danville, Pennsylvania 17822
United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania 19104
United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania 15224
United States
Rhode Island Hospital
Providence, Rhode Island 02903
United States
Prisma Health Richland Hospital
Columbia, South Carolina 29203
United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina 29605
United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota 57117-5134
United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee 37232
United States
Dell Children's Medical Center of Central Texas
Austin, Texas 78723
United States
Driscoll Children's Hospital
Corpus Christi, Texas 78411
United States
Medical City Dallas Hospital
Dallas, Texas 75230
United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas 75390
United States
El Paso Children's Hospital
El Paso, Texas 79905
United States
Children's Hospital of San Antonio
San Antonio, Texas 78207
United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas 78229
United States
University of Virginia Cancer Center
Charlottesville, Virginia 22908
United States
Children's Hospital of The King's Daughters
Norfolk, Virginia 23507
United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia 23298
United States
Seattle Children's Hospital
Seattle, Washington 98105
United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington 99204
United States
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington 98405
United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin 53792
United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin 54449
United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin 53226
United States
IWK Health Centre
Halifax, Nova Scotia B3K 6R8
Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec H3T 1C5
Canada
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec J1H 5N4
Canada
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, G1V 4G2
Canada