Risk-Directed Therapy for Medulloblastoma

Recruiting in Palo Alto (17 mi)

+22 other locations

Dr. Giles W. Robinson, MD | Memphis, TN ...

Overseen byAmar Gajjar, MD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: St. Jude Children's Research Hospital

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?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)

Eligibility Criteria

This trial is for individuals aged 3-22 with newly diagnosed medulloblastoma, or those up to age 40 with SHH subtype. They must have had surgery within the last 36 days and not received prior brain tumor treatments. Good performance status is required, and women of childbearing potential must not be pregnant.

Inclusion Criteria

Biological parent(s) of participant enrolling on this protocol

My health status meets the required level for my age.

My age fits the trial's requirements for my specific diagnosis and treatment plan.

+4 more

Exclusion Criteria

Other clinically significant medical disorders that could compromise ability to tolerate protocol therapy

My brain tumor is not a medulloblastoma or PNET located in the back of my brain.

I am eligible for the Stratum S maintenance chemotherapy.

+2 more

Participant Groups

The study tests a tailored treatment approach based on both clinical risk (low to high) and molecular subtype (WNT, SHH, Non-WNT/Non-SHH) of medulloblastoma. It involves varying doses of radiation and chemotherapy including cyclophosphamide, cisplatin, vincristine; targeted drugs like vismodegib; new agents pemetrexed, gemcitabine; plus supportive therapies such as aerobic training and neurocognitive remediation.

8Treatment groups

Experimental Treatment

Group I: Stratum W3: High RiskExperimental Treatment6 Interventions

Participants in stratum W3 will undergo high dose craniospinal radiation with boost to the primary tumor site once daily 5 days a week for 6 weeks. Six weeks after completion of radiotherapy, patients receive one cycle of chemotherapy (cisplatin, vincristine, cyclophosphamide) once every 4 weeks for 4 cycles in absence of unacceptable toxicity. Some participants will complete aerobic training and/or neurocognitive remediation.

Group II: Stratum W2: AtypicalExperimental Treatment6 Interventions

Participants in stratum W2 will undergo standard dose craniospinal radiation with boost to the primary tumor site once daily 5 days a week for 6 weeks. Six weeks after completion of radiotherapy, patients receive one cycle of chemotherapy (cisplatin, vincristine, cyclophosphamide) once every 4 weeks for 4 cycles in absence of unacceptable toxicity. Some participants will complete aerobic training and/or neurocognitive remediation.

Group III: Stratum W1: Low RiskExperimental Treatment6 Interventions

Participants in stratum W1 will undergo reduced dose Craniospinal Irradiation with boost to the primary tumor site once daily 5 days a week for 6 weeks. Six weeks after completion of radiotherapy, patients receive one cycle of chemotherapy (cisplatin, vincristine, cyclophosphamide) once every 4 weeks for 4 cycles in absence of unacceptable toxicity. Some participants will complete aerobic training and/or neurocognitive remediation.

Group IV: Stratum S2: High RiskExperimental Treatment7 Interventions

Participants in stratum S2 will undergo high dose craniospinal radiation with boost to the primary tumor site once daily 5 days a week for 6 weeks. Six weeks after completion of radiotherapy, patients receive one cycle of chemotherapy (cisplatin, vincristine, cyclophosphamide) once every 4 weeks for 4 cycles in absence of unacceptable toxicity. After completion of 4 cycles of chemotherapy, participants who are skeletally mature will receive maintenance chemotherapy with vismodegib. Some participants will complete aerobic training and/or neurocognitive remediation.

Group V: Stratum S1: Standard RiskExperimental Treatment7 Interventions

Participants in stratum S1 will undergo standard dose craniospinal radiation with boost to the primary tumor site once daily 5 days a week for 6 weeks. Six weeks after completion of radiotherapy, patients receive one cycle of chemotherapy (cisplatin, vincristine, cyclophosphamide) once every 4 weeks for 4 cycles in absence of unacceptable toxicity. After completion of 4 cycles of chemotherapy, participants who are skeletally mature will receive maintenance chemotherapy with vismodegib. Some participants will complete aerobic training and/or neurocognitive remediation.

Group VI: Stratum N3: High RiskExperimental Treatment8 Interventions

Participants in stratum N3 will undergo high dose craniospinal radiation with boost to the primary tumor site once daily 5 days a week for 6 weeks. Six weeks after completion of radiotherapy, patients receive standard chemotherapy (cisplatin, vincristine, cyclophosphamide) for 4 cycles intermixed with an additional 3 cycles of chemotherapy with pemetrexed and gemcitabine in absence of unacceptable toxicity. Some participants will complete aerobic training and/or neurocognitive remediation.

Group VII: Stratum N2: Intermediate RiskExperimental Treatment8 Interventions

Participants in stratum N2 will undergo standard dose craniospinal radiation with boost to the primary tumor site once daily 5 days a week for 6 weeks. Six weeks after completion of radiotherapy, patients receive standard chemotherapy (cisplatin, vincristine, cyclophosphamide) for 4 cycles intermixed with an additional 3 cycles of chemotherapy with pemetrexed and gemcitabine in absence of unacceptable toxicity. Some participants will complete aerobic training and/or neurocognitive remediation.

Group VIII: Stratum N1: Standard RiskExperimental Treatment6 Interventions

Participants in stratum N1 will undergo standard dose craniospinal radiation with boost to the primary tumor site once daily 5 days a week for 6 weeks. Six weeks after completion of radiotherapy, patients receive one cycle of chemotherapy (cisplatin, vincristine, cyclophosphamide) once every 4 weeks for 4 cycles in absence of unacceptable toxicity. Some participants will complete aerobic training and/or neurocognitive remediation.

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺 Approved in European Union as Platinol for: