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NCT05382338PHASE3Recruiting

A Study of Treatment for Medulloblastoma Using Sodium Thiosulfate to Reduce Hearing Loss

Children's Oncology Group

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

Inclusion Criteria: * PRE-ENROLLMENT: Patients must be ≥ 4 years and ≤ 21 years of age at the time of enrollment * PRE-ENROLLMENT: Patient is suspected to have newly-diagnosed medulloblastoma by institutional diagnosis * Please note: Patients with a pending result of CSF cytology tests are eligible for NCI-2014-02057 (APEC14B1-Central Nervous System \[CNS\]) and CNS/Medulloblastoma Pre Enrollment Eligibility Screening * PRE-ENROLLMENT: The patient and/or their parents or legal guardians must have signed informed consent for APEC14B1 Part A - Eligibility Screening and consent for the Molecular Characterization Initiative (MCI) * PRE-ENROLLMENT: The required specimens are projected to be submitted under APEC14B1-CNS as soon as possible, preferably within 5 days of definitive surgery * PRE-ENROLLMENT: All patients must have rapid central pathology review under APEC14B1-CNS prior to study enrollment on ACNS2031 step 1 in order to avoid discordant diagnoses and to verify diagnosis criterion for treatment on ACNS2031. * Note: Patients with a pending result of CSF cytology tests are eligible for the rapid central pathology screening review. Confirmation of CSF negativity is needed for enrollment on the ACNS2031 protocol * PRE-ENROLLMENT: All patients must have rapid central molecular screening review under APEC14B1-CNS prior to study enrollment on ACNS2031 step 1, in order to avoid discordant diagnoses and to verify diagnosis criterion for treatment on ACNS2031 * PRE-ENROLLMENT: All patients who have histopathology confirmed must have rapid central imaging screening review under APEC14B1 prior to study enrollment on ACNS2031 step 1 * Note: Patients must not have metastatic disease on cranial or spinal MRI. Patients with \> 1.5 cm\^2 residual tumor after initial surgical resection may undergo a second surgical resection prior to subsequent therapy to render them eligible for this study. The day of the second resection to remove residual tumor will be regarded as the day of definitive surgery (Day 0) and must be within a month (31 days) of the initial resection * PRE-ENROLLMENT: All patients who have histopathology confirmed must have rapid central audiology review under APEC14B1-CNS prior to study enrollment on ACNS2031 step 1 * Patients must be \>= 4 years and =\< 21 years of age at the time of enrollment * Patients must be newly diagnosed and have eligibility confirmed by rapid central pathology and molecular screening reviews performed on APEC14B1 and via the Molecular Characterization Initiative * Average-risk cohort * Clinico-pathologic criteria: * M0 disease * No diffuse anaplastic histology AND * Molecular criteria: * SHH, p53wt, GLI2 normal, MYCN normal, no chromosome 14q loss * Group 3, MYC normal, no isochromosome 17q * Group 4, no chromosome 11 loss * Low-risk features cohort * Clinico-pathologic criteria: * M0 disease * No diffuse anaplastic histology AND * Molecular criteria: * Group 4, chromosome 11 loss * Patients must have negative lumbar CSF cytology * Note: CSF cytology for staging should be performed no sooner than 14 days post operatively to avoid false positive CSF. Ideally, CSF should be obtained between day 14 and day 21 to allow for final staging status before enrollment onto the study. Patients with positive CSF cytology obtained 0 to 14 days after surgery should have cytology repeated to determine eligibility and final CSF status. Patients with negative CSF cytology from lumbar puncture obtained 0 to 14 days after surgery do not need cytology repeated. Patients with negative CSF cytology from lumbar puncture obtained prior to surgery do not need cytology repeated post-operatively * Patients must have eligibility confirmed by Rapid Central Imaging Review performed on APEC14B1. Patients must have =\< 1.5 cm\^2 cross-sectional area of residual tumor. Whole brain MRI with and without gadolinium and spine MRI with gadolinium must be performed * Patients must weigh \> 10 kg * Patients must be enrolled, and protocol therapy must be projected to begin, no later than 31 days after definitive diagnostic surgery (day 0) * Peripheral absolute neutrophil count (ANC) \>= 1000/uL (within 7 days prior to enrollment) * Platelet count \>= 100,000/uL (transfusion independent) (within 7 days prior to enrollment) * Hemoglobin \>= 8.0 g/dL (may receive red blood cell count \[RBC\] transfusions) (within 7 days prior to enrollment) * A serum creatinine (within 7 days prior to enrollment) based on age/sex as follows: * 4 to \< 6 years (age); 0.8 mg/dL (male) 0.8 mg/dL (female) * 6 to \< 10 years (age); 1 mg/dL (male) 1 mg/dL (female) * 10 to \< 13 years (age); 1.2 mg/dL (male) 1.2 mg/dL (female) * 13 to \< 16 years (age); 1.5 mg/dL (male) 1.4 mg/dL (female) * \>= 16 years (age); 1.7 mg/dL (male) 1.4 mg/dL (female) OR a 24 hour urine Creatinine clearance \>= 70 mL/min/1.73 m\^2 (within 7 days prior to enrollment) OR a glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 (within 7 days prior to enrollment). GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard) * Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility * Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment) * Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (within 7 days prior to enrollment) * Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L * 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 epilepticus, a coma or assisted ventilation at the time of study enrollment * Auditory function defined as: * Patients must have normal hearing (defined as International Society of Pediatric Oncology \[SIOP\] grade 0) in at least one ear confirmed by rapid central audiology review performed on APEC14B1 prior to enrollment * 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 Exclusion Criteria: * Patients with metastatic disease by either MRI evaluation or lumbar CSF cytology are not eligible. Patients who are unable to undergo a lumbar puncture for assessment of CSF cytology are ineligible * Patients must not have received any prior radiation therapy or chemotherapy (tumor-directed therapy) other than surgical intervention and/or corticosteroids * Patients must not have any known hypersensitivity to STS, sulfates/sulfites, or other thiol agents (e.g., amifostine, n-acetylcysteine, MESNA, and captopril) * Pregnancy and Breastfeeding: * Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential * Lactating females who plan to breastfeed their infants * Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

Interventions

PROCEDURE

Audiometric Test

PROCEDURE

Auditory Brainstem Response

PROCEDURE

Biospecimen Collection

DRUG

Cisplatin

DRUG

Cyclophosphamide

DRUG

Lomustine

PROCEDURE

Magnetic Resonance Imaging

OTHER

Quality-of-Life Assessment

RADIATION

Radiation Therapy

DRUG

Sodium Thiosulfate

OTHER

Survey Administration

DRUG

Vincristine

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Conditions

Childhood Medulloblastoma

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