RECRUITING

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

Conditions

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase 3 Study of Sodium Thiosulfate for Reduction of Cisplatin-Induced Ototoxicity in Children With Average-Risk Medulloblastoma and Reduced Therapy in Children With Medulloblastoma With Low-Risk Features

Quick Facts

Study Start:2023-02-20

Study Completion:2027-12-20

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05382338

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:4 Years to 21 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Principal Investigator

Ralph Salloum

PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Study Locations (Sites)

Children's Hospital of Alabama

Birmingham, Alabama, 35233

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

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

Alfred I duPont Hospital for Children

Wilmington, Delaware, 19803

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

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

University of Illinois

Chicago, Illinois, 60612

United States

Riley Hospital for Children

Indianapolis, Indiana, 46202

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

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109

United States

Children's Hospital of Michigan

Detroit, Michigan, 48201

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

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

Saint Louis, Missouri, 63104

United States

Washington University School of Medicine

Saint Louis, Missouri, 63110

United States

Saint Peter's University Hospital

New Brunswick, New Jersey, 08901

United States

Saint Joseph's Regional Medical Center

Paterson, New Jersey, 07503

United States

Albany Medical Center

Albany, New York, 12208

United States

Montefiore Medical Center - Moses Campus

Bronx, New York, 10467

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

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

New York Medical College

Valhalla, New York, 10595

United States

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599

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

Oregon Health and Science University

Portland, Oregon, 97239

United States

Geisinger Medical Center

Danville, Pennsylvania, 17822

United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224

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

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

Virginia Commonwealth University/Massey 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

Collaborators and Investigators

Sponsor: Children's Oncology Group

Ralph Salloum, PRINCIPAL_INVESTIGATOR, Children's Oncology Group

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-02-20

Study Completion Date2027-12-20

Study Record Updates

Study Start Date2023-02-20

Study Completion Date2027-12-20

Terms related to this study

Additional Relevant MeSH Terms

Childhood Medulloblastoma