Treatment of Patients With Newly Diagnosed Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor

Summary

Drugs used in chemotherapy, such as vincristine, cisplatin, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. Autologous stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy or radiation therapy. It is not yet known which radiation therapy regimen combined with chemotherapy and donor stem cell transplant is more effective in treating medulloblastoma, supratentorial primitive neuroectodermal tumor, or atypical teratoid rhabdoid tumor. This phase III trial is studying two different regimens of radiation therapy when given together with chemotherapy and autologous stem cell transplant to see how well they work in treating patients with newly diagnosed medulloblastoma, supratentorial primitive neuroectodermal tumor, or atypical teratoid rhabdoid tumor. PRIMARY OBJECTIVE: * To assess the relationship between ERBB2 protein expression in tumors and progression-free survival probability for patients with medulloblastoma. * To estimate the frequency of mutations associated with SHH and WNT tumors (as defined by gene expression profiling) via targeted sequencing performed in an independent cohort of WNT and SHH tumors (also defined by gene expression profiling).

Timeline

Start

2003-08

Primary completion

2016-12

Completion

2023-12-31

Publications

• Acharya S, Guo Y, Patni T, Li Y, Wang C, Gargone M, Ashford JM, Wilson L, Faught A, Reddick WE, Patay Z, Gajjar A, Conklin HM, Merchant TE. Association Between Brain Substructure Dose and Cognitive Outcomes in Children With Medulloblastoma Treated on SJMB03: A Step Toward Substructure-Informed Planning. J Clin Oncol. 2022 Jan 1;40(1):83-95. doi: 10.1200/JCO.21.01480. Epub 2021 Oct 29.
• Partanen M, Anghelescu DL, Hall L, Schreiber JE, Rossi M, Gajjar A, Jacola LM. Longitudinal associations between exposure to anesthesia and neurocognitive functioning in pediatric medulloblastoma. Eur J Cancer. 2021 May;148:103-111. doi: 10.1016/j.ejca.2021.02.010. Epub 2021 Mar 17.
• Kumar R, Smith KS, Deng M, Terhune C, Robinson GW, Orr BA, Liu APY, Lin T, Billups CA, Chintagumpala M, Bowers DC, Hassall TE, Hansford JR, Khuong-Quang DA, Crawford JR, Bendel AE, Gururangan S, Schroeder K, Bouffet E, Bartels U, Fisher MJ, Cohn R, Partap S, Kellie SJ, McCowage G, Paulino AC, Rutkowski S, Fleischhack G, Dhall G, Klesse LJ, Leary S, Nazarian J, Kool M, Wesseling P, Ryzhova M, Zheludkova O, Golanov AV, McLendon RE, Packer RJ, Dunham C, Hukin J, Fouladi M, Faria CC, Pimentel J, Walter AW, Jabado N, Cho YJ, Perreault S, Croul SE, Zapotocky M, Hawkins C, Tabori U, Taylor MD, Pfister SM, Klimo P Jr, Boop FA, Ellison DW, Merchant TE, Onar-Thomas A, Korshunov A, Jones DTW, Gajjar A, Ramaswamy V, Northcott PA. Clinical Outcomes and Patient-Matched Molecular Composition of Relapsed Medulloblastoma. J Clin Oncol. 2021 Mar 1;39(7):807-821. doi: 10.1200/JCO.20.01359. Epub 2021 Jan 27.
• Gajjar A, Robinson GW, Smith KS, Lin T, Merchant TE, Chintagumpala M, Mahajan A, Su J, Bouffet E, Bartels U, Schechter T, Hassall T, Robertson T, Nicholls W, Gururangan S, Schroeder K, Sullivan M, Wheeler G, Hansford JR, Kellie SJ, McCowage G, Cohn R, Fisher MJ, Krasin MJ, Stewart CF, Broniscer A, Buchhalter I, Tatevossian RG, Orr BA, Neale G, Klimo P Jr, Boop F, Srinivasan A, Pfister SM, Gilbertson RJ, Onar-Thomas A, Ellison DW, Northcott PA. Outcomes by Clinical and Molecular Features in Children With Medulloblastoma Treated With Risk-Adapted Therapy: Results of an International Phase III Trial (SJMB03). J Clin Oncol. 2021 Mar 1;39(7):822-835. doi: 10.1200/JCO.20.01372. Epub 2021 Jan 6.
• Xu H, Robinson GW, Huang J, Lim JY, Zhang H, Bass JK, Broniscer A, Chintagumpala M, Bartels U, Gururangan S, Hassall T, Fisher M, Cohn R, Yamashita T, Teitz T, Zuo J, Onar-Thomas A, Gajjar A, Stewart CF, Yang JJ. Common variants in ACYP2 influence susceptibility to cisplatin-induced hearing loss. Nat Genet. 2015 Mar;47(3):263-6. doi: 10.1038/ng.3217. Epub 2015 Feb 9.

Drugs

Indications