NCT01261429

Study of Nilotinib Efficacy in Pigmented Villo-Nodular Synovitis/ Tenosynovial Giant Cell Tumour (PVNS/TGCT)

Phase II Study of Nilotinib Efficacy in Pigmented Villo-Nodular Synovitis/ Tenosynovial Giant Cell Tumour (PVNS/TGCT)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (actual)
• Sponsor: Centre Leon Berard · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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. 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

Detailed description

A key secondary objective of the study will be to determine the efficacy of 24 weeks (6 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 key secondary objective was defined for the purpose of a further analysis (not described in this protocol) which will pool the data of the PVNS study with those of a similar concomitant study conducted in the US and Australia. The other secondary objectives will be: To evaluate the efficacy of nilotinib according to: * The objective tumour response rate (Complete response + Partial Response according to RECIST version 1.1) after 12 weeks of treatment * The duration of treatment response * The best overall response obtained during the study * The progression-free survival (PFS) * The time to progression (TTP) * The time to treatment failure (TTF) * The proportion of patients with an operable tumour after nilotinib exposure according to investigator evaluation * The description of concomitant treatments use * The correlation between trough levels of nilotinib and objective tumour response To assess the safety of nilotinib for PVNS/TGCT patients 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

Conditions

• Pigmented Villonodular Synovitis

Interventions

Type	Name	Description
DRUG	Tasigna	The study drug is nilotinib (Tasigna®). All patients will be administered with nilotinib 400 mg twice a day for one year. The patient will begin the treatment the day of inclusion. The prescribed dose should be swallowed whole with a glass of water. Doses of 400 mg should be administered twice daily approximately 12 hours apart. Patients should not eat within two hours before and one hour after taking nilotinib and need to avoid foods such as grapefruit juice which may inhibit CYP3A4 enzymes.

Timeline

• Start date: 2010-12-01
• Primary completion: 2013-04-01
• Completion: 2013-04-01
• First posted: 2010-12-16
• Last updated: 2013-04-16

Locations

15 sites across 5 countries: France, Italy, Netherlands, Poland, United Kingdom