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
Nilotinib is a drug that is used to treat a form of a blood cancer called leukemia. Nilotinib works by blocking the action of a protein that might be important for the growth of pigmented villonodular synovitis (PVNS). In this research study the investigators are testing whether nilotinib can stop the growth of PVNS or improve the symptoms experienced from PVNS.
In this research study, each cycle of study drug dosing will last 4 weeks (28 days). During each cycle, participants will take nilotinib by mouth twice daily. During the first cycle, participants will come to the clinic on Days 1 and 8. For Cycles 2-4 and every 3 cycles thereafter, they will come to the clinic on Day 1.
The following tests and procedures will be performed at specific time points during study treatment: MRI or CT scans; physical examinations; vital signs; blood work; questionnaires and EKG.
Participants may continue in this research study for as long as they do not have serious side effects or their disease does not get worse.
Primary Outcome Measures:
Progression free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To estimate progression free survival at 6 months in participants with recurrent PVNS treated with nilotinib.
Secondary Outcome Measures:
Overall tumor response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To determine overall tumor response rate [% complete response + % partial response by RECIST 1.1]
Global principal investigator
Professor David THOMAS (The Kinghorn Cancer Centre and Peter MacCallum Cancer Centre, Australia)
Professor Isabelle Ray-Coquard (Centre Leon-Berard, France)
Professor Ian Judson and Dr Beatrice Seddon (Royal Marsden Hospital and
University College London Hospital, UK)
Professor Ajay Puri (Tata Memorial Hospital, India)
Professor Bob Maki and Dr Josh Schiffman (Mount Sinai Medical Centre and Huntsman Cancer Institute, US)