A Clinical and Molecular Risk-Directed Therapy for Newly Diagnosed Medulloblastoma

Running, not enrolling · Phase 2

Conditions studied: Medulloblastoma

In brief

Historically, medulloblastoma treatment has been determined by the amount of leftover disease present after surgery, also known as clinical risk (standard vs. high risk). Recent studies have shown that medulloblastoma is made up of distinct molecular subgroups which respond differently to treatment. This suggests that clinical risk alone is not adequate to identify actual risk of recurrence. In order to address this, we will stratify medulloblastoma treatment in this phase II clinical trial based on both clinical risk (low, standard, intermediate, or high risk) and molecular subtype (WNT, SHH, or Non-WNT Non-SHH). This stratified clinical and molecular treatment approach will be used to evaluate the following: * To find out if participants with low-risk WNT tumors can be treated with a lower dose of radiation to the brain and spine, and a lower dose of the chemotherapy drug cyclophosphamide while still achieving the same survival rate as past St. Jude studies with fewer side effects. * To find out if adding targeted chemotherapy after standard chemotherapy will benefit participants with SHH positive tumors. * To find out if adding new chemotherapy agents to the standard chemotherapy will improve the outcome for intermediate and high risk Non-WNT Non-SHH tumors. * To define the cure rate for standard risk Non-WNT Non-SHH tumors treated with reduced dose cyclophosphamide and compare this to participants from the past St. Jude study. All participants on this study will have surgery to remove as much of the primary tumor as safely possible, radiation therapy, and chemotherapy. The amount of radiation therapy and type of chemotherapy received will be determined by the participant's treatment stratum. Treatment stratum assignment will be based on the tumor's molecular subgroup assignment and clinical risk. The participant will be assigned to one of three medulloblastoma subgroups determined by analysis of the tumor tissue for tumor biomarkers: * WNT (Strata W): positive for WNT biomarkers * SHH (Strata S): positive for SHH biomarkers * Non-WNT Non-SHH, Failed, or Indeterminate (Strata N): negative for WNT and SHH biomarkers or results are indeterminable Participants will then be assigned to a clinical risk group (low, standard, intermediate, or high) based on assessment of: * How much tumor is left after surgery * If the cancer has spread to other sites outside the brain \[i.e., to the spinal cord or within the fluid surrounding the spinal cord, called cerebrospinal fluid (CSF)\] * The appearance of the tumor cells under the microscope * Whether or not there are chromosomal abnormalities in the tumor, and if present, what type (also called cytogenetics analysis)

Key facts

Study ID: NCT01878617
Run by: St. Jude Children's Research Hospital
People needed: 660
Starts: 2013-06-23
Expected to finish: 2031-10-13
Last updated by the study team: 2025-11-13

Who can join

Age: 3 and older, up to 39. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Medulloblastoma or medulloblastoma variants including posterior fossa PNET as documented by an institutional pathologist.
Participant's age meets one of the following: (1) Age greater than or equal to 3 years and less than 22 years of age at the time of diagnosis (may enroll on Strata W, S or N), OR (2) age is greater than or equal to 22 years and less than 40 years AND patient has SHH medulloblastoma (must enroll on Stratum S).
No previous radiotherapy, chemotherapy or other brain tumor directed therapy other than corticosteroid therapy and surgery.
Patients must begin treatment as outlined in the protocol within 36 days of definitive surgery (day of surgery is day 0; definitive surgery includes second surgeries to resect residual tumor).
Adequate performance status: children < 10-Lansky Score ≥ 30; children ≥ 10-Karnofsky ≥ 30 (except for posterior fossa syndrome).
Females of child-bearing potential cannot be pregnant or breast-feeding. Female participants > 10 years of age or post-menarche must have a negative serum or urine pregnancy test prior to enrollment.
Biological parent(s) of participant (child) enrolling on this protocol. These parents will be assigned to cohort P. The exclusion criteria below do not apply to this cohort.

You may not qualify if…

CNS embryonal tumor other than medulloblastoma or PNET in the posterior fossa, for example, patients with diagnosis of Atypical Teratoid / Rhabdoid Tumor (ATRT), supratentorial PNET, pineoblastoma, ependymoblastoma, ETANTR are excluded.
Research participants with other clinically significant medical disorders that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results history.
Participants in the Stratum S maintenance chemotherapy portion of the study must meet the criteria below prior to start of vismodegib therapy:
Participants must be Stratum S (SHH)
Participants must be skeletally mature defined as females with a bone age ≥ 15 years and males with a bone age ≥ 17 years.
Must be able to swallow pills
BSA must be >0.67 and <2.5 m2
Male and female participants of reproductive potential must agree to effective contraception during and after study treatment. See Appendices I and II for further guidance for participants receiving vismodegib
ANC ≥ 1000/mm\^3 (after G-CSF discontinued)
Platelets ≥ 50,000/mm\^3 (without support)
Hgb ≥ 8 g/dL (with or without transfusion support)
Serum creatinine ≤ 1.5 mg/dL
Total bilirubin ≤ 1.5X the institutional ULN
SGPT (ALT) ≤ 2.5X the institutional ULN
SGOT (AST) ≤ 2.5X the institutional ULN
Alkaline Phosphatase ≤ 1.5X the institutional ULN
Serum albumin ≥ 2.5 g/dL
Participants in the exercise intervention portion of the study must meet all criteria below:
Must be ≥ 5 years and < 22 years at the time of enrollment
Must have no congenital heart disease
Must be capable of performing the exercise intervention at the time of baseline assessment as determined by the treating physician.
Participants in the cognitive remediation intervention portion of the study must meet all criteria below:
Completed protocol-directed radiation therapy
≥5 years at the time of remediation intervention consent or age is greater than or equal to 22 years and less than 40 years and patient has SHH medulloblastoma
English as primary language and training aide who speaks English available to participate in required sessions

Where it is running

Lucille Packard Children's Hospital at Stanford University Medical Center — Palo Alto, California, United States
Rady Children's Hospital — San Diego, California, United States
Yale University — New Haven, Connecticut, United States
Children's National Medical Center — Washington D.C., District of Columbia, United States
University of Florida — Gainesville, Florida, United States
Arnold Palmer Hospital for Children — Orlando, Florida, United States
Children's Hospital and Clinics of Minnesota — Minneapolis, Minnesota, United States
Duke Children's Hospital and Health Center — Durham, North Carolina, United States
Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States
Medical University of South Carolina — Charleston, South Carolina, United States
St. Jude Children's Research Hospital — Memphis, Tennessee, United States
University of Texas Southwestern Medical Center — Dallas, Texas, United States
Cook Children's Medical Center — Fort Worth, Texas, United States
Texas Children's Cancer Center — Houston, Texas, United States
Sydney Children's Hospital — Randwick, New South Wales, Australia
Children's Hospital at Westmead — Westmead, New South Wales, Australia
Queensland Children's Hospital — Brisbane, Queensland, Australia
Royal Children's Hospital, Melbourne — Melbourne, Victoria, Australia
Perth Children's Hospital — Perth, Western Australia, Australia
Alberta Children's Hospital — Calgary, Alberta, Canada
The Hospital for Sick Children — Toronto, Ontario, Canada
Centre Hospitalier Universitaire Sainte-Justine — Montreal, Quebec, Canada
Starship Children's Hospital — Auckland, New Zealand

Full record on ClinicalTrials.gov

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