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Clinical Trial
. 2013 Sep;15(9):1236-43.
doi: 10.1093/neuonc/not097. Epub 2013 Jul 14.

Phase II study of irinotecan in combination with temozolomide (TEMIRI) in children with recurrent or refractory medulloblastoma: a joint ITCC and SIOPE brain tumor study

Jacques Grill  1 , Birgit Geoerger, Lyle Gesner, Danuta Perek, Pierre Leblond, Adela Cañete, Isabelle Aerts, Luis Madero, Josep Sanchez de Toledo Codina, Joris Verlooy, Edward Estlin, Laura Cisar, Aurora Breazna, Andrew Dorman, Simon Bailey, Gary Nicolin, Richard G Grundy, Darren Hargrave; European Consortium Innovative Therapies for Children with Cancer (ITCC) and the European Society for Paediatric Oncology (SIOPE) brain tumor group
Affiliations
Clinical Trial

Phase II study of irinotecan in combination with temozolomide (TEMIRI) in children with recurrent or refractory medulloblastoma: a joint ITCC and SIOPE brain tumor study

Jacques Grill et al. Neuro Oncol. 2013 Sep.

Abstract

Background: This multicenter phase II study investigated temozolomide + irinotecan (TEMIRI) treatment in children with relapsed or refractory medulloblastoma.

Methods: Patients received temozolomide 100-125 mg/m(2)/day (days 1-5) and irinotecan 10 mg/m(2)/day (days 1-5 and 8-12) every 3 weeks. The primary endpoint was tumor response within the first 4 cycles confirmed ≥4 weeks and assessed by an external response review committee (ERRC). In a 2-stage Optimum Simon design, ≥6 responses in the first 15 evaluable patients were required within the first 4 cycles for continued enrollment; a total of 19 responses from the first 46 evaluable patients was considered successful.

Results: Sixty-six patients were treated. Seven responses were recorded during stage 1 and 15 in the first 46 ERRC evaluated patients (2 complete responses and 13 partial responses). The objective response rate during the first 4 cycles was 32.6% (95% confidence interval [CI], 19.5%-48.0%). Median duration of response was 27.0 weeks (7.7-44.1 wk). In 63 patients evaluated by local investigators, the objective response rate was 33.3% (95% CI, 22.0%-46.3%), and 68.3% (95% CI, 55.3%-79.4%) experienced clinical benefit. Median survival was 16.7 months (95% CI, 13.3-19.8). The most common grade 3 treatment-related nonhematologic adverse event was diarrhea (7.6%). Grade 3/4 treatment-related hematologic adverse events included neutropenia (16.7%), thrombocytopenia (12.1%), anemia (9.1%), and lymphopenia (9%).

Conclusions: The planned study primary endpoint was not met. However, its tolerability makes TEMIRI a suitable candidate chemotherapy backbone for molecularly targeted agents in future trials in this setting.

Keywords: TEMIRI; medulloblastoma; temozolomide.

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