An open-label international multicentric phase II study of nilotinib in progressive pigmented villo-nodular synovitis (PVNS) not amenable to a conservative surgical treatment.

Abstract

10006 Background: PVNS, also known as tenosynovial giant cell tumor (TGCT), is a rare pathological entity affecting the synovium in young adults. This neoplastic disease is driven by a t(1;2) translocation which results in the fusion of COL6A3 and M-CSF genes. Nilotinib has inhibitory properties on M-CSF receptor pathway which could be of therapeutic interest in pts with non resectable PVNS. Methods: In this open-label International, multicenter, non-randomized, phase II study the primary objective is to evaluate the efficacy of nilotinib treatment in patients (pts) with progressive or relapsing PVNS not amenable to surgery or in whom surgery would be mutilating, as measured by the 12-week progression-free rate (12-w PFR) validated by an independent committee. Using a Bayesian design with a stopping rule for futility, interim analyses were planned after the inclusion of 10 pts and then every 5 pts. Results: From December 2010 to November 2011, 33 pts with progressive disease from 17 institutions from Europe and Australia were enrolled. 14 pts (median age 37 y (range: 19-68), 7 males) were analyzed in the 2nd interim analysis. Median time since diagnosis was 4.4 years (range: 0.2-26). Primary tumour was located on a knee for 10 pts (71%) and on hip (1 pt, 7%), finger (7%), foot (7%), hand (7%), respectively. 69% of pts had a inoperable PVNS and 31% had a resectable tumour but requiring mutilating surgery. All pts started nilotinib at the planned dose of 800 mg/day. At a median follow-up of 8.9 months (range: 0.6-11), 2 pts had a dose reduction and 1 pt had discontinued nilotinib after 14 days due to toxicity. Nilotinib was well tolerated, with only 2 pts experiencing grade 3 adverse events (anorexia: 1 pt; hepatic failure: 1 pt).The 12-w PFR was 85.7% (95%CI, 57.2%-98.2%), in favour of the study continuation. No OR was observed at w-12; 1 pt (7%) was in PR at w-30. Updated results will be presented after the 3rd interim analysis. Conclusions: Nilotinib treatment induces disease stabilisation in a large proportion of PVNS patients with non resectable disease or in whom resection would be mutilating.