Protocol Summary

Protocol No.: OCR15132

Sponsor Protocol No.: SJMB12

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

Principal Investigator(s)
Gururangan, Sridharan

Objective
This study is designed to treat participants according to both their clinical risk and their molecular sub-type. By doing so, this study will try to determine if different doses of radiation and the use of targeted chemotherapy will benefit participants based on the their individual risk and molecular make-up.

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.

Phase: Phase II

Age Group: Children

Scope: National

Treatment
Patients are stratified according to molecular subgroup (WNT, SHH, or Non-WNT Non- SHH) and then by clinical risk (extent of resection, M stage, histologic subtype, and cytogenetic features). All patients will be treated with risk-adapted radiation therapy and adjuvant chemotherapy. Patients assigned to Stratum W1 will receive reduced dose radiation therapy. Patients assigned to Stratum W2, S1, N1, or N2 will receive standard dose radiation therapy. Patients assigned to Stratum W3, S2, or N3 will receive high dose radiation therapy. Radiation therapy will be followed by 4 cycles of adjuvant chemotherapy with cyclophosphamide, cisplatin and vincristine for all patients. Patients assigned to Stratum N2 or N3 (Non-WNT Non-SHH with high risk factors) will receive 3 cycles of pemetrexed and gemcitabine chemotherapy intermixed into the adjuvant chemotherapy cycles. Patients with SHH subtype (Stratum S1 or S2) who are skeletally mature will receive 12 months additional maintenance therapy with vismodegib.

Detailed Eligibility
INCLUSION CRITERIA:
1. Age greater than or equal to 3 years and less than 22 years of age at the time of diagnosis.
2. Medulloblastoma or medulloblastoma variants including posterior fossa PNET as documented by an institutional pathologist.
3. No previous radiotherapy, chemotherapy or other brain tumor directed therapy other than corticosteroid therapy and surgery.
4. 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).
5. Adequate performance status: children 6. 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.
7. 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.

EXCLUSION CRITERIA:
1. 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.
2. 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:
- Must be > 10 years at the time of start of maintenance
- Must be skeletally mature defined as females with a bone age ≥ 15 years and males with a bone age ≥ 17 years
- Must agree to effective contraception if participant has reproductive potential

Participants in the exercise intervention portion of the study must meet all criteria below:
- Must be > 5 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
- English as primary language and training aide who speaks English available to participate in required sessions
- No significant cognitive impairment operationalized as either an IQ - No major sensory or motor impairment that would preclude valid cognitive testing (e.g., unresolved posterior fossa syndrome, blindness, poorly controlled seizures/photosensitive epilepsy, psychosis) or a major psychological condition that would preclude completion of the intervention (e.g., significant oppositionality, autism spectrum disorder, severe anxiety or depressive symptoms)

Applicable Disease Sites
Brain and Nervous System
Pediatric (Childhood) Cancer

Participating Institutions
UF Gainesville

More Information:
View study listing on ClinicialTrials.gov
http://www.clinicaltrials.gov/ct2/show/
NCT01878617