Description
The purpose of this study is to explore the efficacy of nilotinib as a treatment of patients with progressive or relapsing pigmented villo-nodular synovitis / tenosynovial giant cell tumour (PVNS/TGCT) who cannot be treated by surgery.
An exploratory objective of the study will be to study the relationship between the objective tumour response and the following tumour characteristics (tissues collected in a prior surgery, or by biopsy, upon specific acceptance by the patient; if no tissue is available in the prior surgery, a biopsy will be done at visit 2):
Presence of COL6A3/CSF1 fusion gene Presence of M-CSF, CSF1R, KIT, PDGFRA and B on immunohistochemistry Presence of phosphorylated c-fms on tumour samples Activation of the PI3K/Akt/mTor pathway, presence of activating mutations of ras, and other potential molecular alterations
The primary objective of the study will be to determine the efficacy of 12 weeks (3 months) of nilotinib treatment as measured by the non progression rate (Complete response + Partial Response + Stable disease according to Response Evaluation Criteria In Solid Tumours – RECIST version 1.1) in patients with progressive or relapsing PVNS/TGCT who cannot be treated by surgery.
this study is an international, multicentre, non-randomized, open-label phase II clinical trial with a Bayesian design.
A maximum sample size of 50 patients will be included in the study
Primary Outcome Measures:
the non progression rate after 12 weeks (3 months) of treatment, based on the response evaluated by CT scan or MRI according to RECIST criteria (RECIST version 1.1) and validated by a central review committee.
Secondary Outcome Measures:
Non progression rate after 24 weeks (6 months) of treatment, based on the response evaluated by CT scan or MRI according to RECIST criteria (RECIST version 1.1).
Objective tumour response according to RECIST version 1.1 (CR and PR) after 12 weeks of treatment
Duration of response
Best overall response
Progression-free survival
Time to progression
Time to treatment failure
Non progression rate after 12 weeks of treatment, based on the response evaluated locally by the investigator in charge using CT scan or MRI and according to RECIST criteria (RECIST version 1.1)
Proportion of patients with an operable tumour after nilotinib exposure according to investigator evaluation
Concomitant treatment use during the study
Correlation between trough level of nilotinib at 6 weeks and 12 weeks and objective tumour response
Safety evaluation will be based on overall safety profile characterized by type, frequency and severity (as graded using NCI-CTCAE V3.0) of adverse events.
NCT01261429