Phase 2 Study Assessing Efficacy and Safety of Crizotinib in Patients Harboring an Alteration on ALK, MET or ROS1

Summary

This is a biology driven, trans-tumoral, multicentric phase II trial assessing the efficacy and the safety of the targeted agent crizotinib as a monotherapy in 23 cohorts of patients with identified activating molecular alterations in the crizotinib target genes. A cohort is defined by a pathology and a crizotinib-target alteration (eg gastric cancer with MET amplification). For each cohort a two-stage design will be implemented. In the situation where expected accrual allows for a sufficient number of patients to be accrued, the alpha and beta errors will be fixed at 10%. However, in very rare diseases, such as inflammatory myofibroblastic tumor (IMT), neuroblastoma, glioblastoma, and rhabdomyosarcoma (RMS), it is anticipated that the target number may not be achievable in a reasonable timeframe; for these cohorts, the alpha and beta errors will be fixed at 15%. Consequently three different statistical designs will be a priori considered according to the expected response rate and incidence.

Timeline

Start

2013-08

Primary completion

2019-06

Completion

2023-12-06

Publications

• Brugieres L, Cozic N, Houot R, Rigaud C, Sibon D, Arfi-Rouche J, Bories P, Cottereau AS, Delmer A, Ducassou S, Garnier N, Lamant L, Leruste A, Millot F, Moalla S, Morschhauser F, Nolla M, Pagnier A, Reguerre Y, Renaud L, Schmitt A, Simonin M, Verschuur A, Hoog Labouret N, Mahier Ait Oukhatar C, Vassal G. Efficacy and safety of crizotinib in ALK-positive systemic anaplastic large-cell lymphoma in children, adolescents, and adult patients: results of the French AcSe-crizotinib trial. Eur J Cancer. 2023 Sep;191:112984. doi: 10.1016/j.ejca.2023.112984. Epub 2023 Jul 17.
• Aparicio T, Cozic N, de la Fouchardiere C, Meriaux E, Plaza J, Mineur L, Guimbaud R, Samalin E, Mary F, Lecomte T, Gomez-Roca C, Haineaux PA, Gratet A, Selves J, Menu Y, Colignon N, Johnson L, Legrand F, Vassal G. The Activity of Crizotinib in Chemo-Refractory MET-Amplified Esophageal and Gastric Adenocarcinomas: Results from the AcSe-Crizotinib Program. Target Oncol. 2021 May;16(3):381-388. doi: 10.1007/s11523-021-00811-8. Epub 2021 Apr 13.
• Moro-Sibilot D, Cozic N, Perol M, Mazieres J, Otto J, Souquet PJ, Bahleda R, Wislez M, Zalcman G, Guibert SD, Barlesi F, Mennecier B, Monnet I, Sabatier R, Bota S, Dubos C, Verriele V, Haddad V, Ferretti G, Cortot A, De Fraipont F, Jimenez M, Hoog-Labouret N, Vassal G. Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSe phase II trial. Ann Oncol. 2019 Dec 1;30(12):1985-1991. doi: 10.1093/annonc/mdz407.

Drugs

Indications