Ph I dose escalation of INC280+food in cMET advanced solid tumors
Research type
Research Study
Full title
A multicenter, open label, Phase 1 dose escalation study to evaluate the pharmacokinetics, safety, and tolerability of INC280 tablet formulation with food in patients with cMET dysregulated advanced solid tumors
IRAS ID
215144
Contact name
Emma Dean
Contact email
Sponsor organisation
Novartis Pharmaceuticals UK Ltd
Eudract number
2016-001829-14
Duration of Study in the UK
1 years, 2 months, days
Research summary
Genetic mutations or alterations may cause cMET molecular signaling pathways to become overactive, triggering tumour growth, in many different cancers including non-small cell lung cancer, renal cell carcinoma and colorectal cancer. INC280 is an orally, bioavailable highly potent and selective cMET inhibitor, capable of blocking cMET activation. Currently, single 600mg doses are well tolerated; when administered with food INC280 exposure is expected to increase by 30%.\nThis study is designed to assess safety and tolerability of INC280 when taken with a high-fat meal in patients with cMET positive cancers. This will be assessed under increasing doses of INC280.\n The first patient group will receive 300mg INC280, twice daily, and will also receive high-fat meals on the morning of Cycle 1 Days 1 and 7. Blood samples will be collected to measure INC280 pharmacokinetics (PK; levels of INC280 in the blood) when taken under high-fat conditions. During the remainder of the study the patients will be given INC280 within 30 minutes of an unrestricted meal type. A minimum of 6 patients will be enrolled at this dose, and, if tolerated, the dose will be escalated to 400mg, twice daily, with food. If this dose is tolerated, approximately 15 PK evaluable patients will be enrolled at the highest dose. \n35 patients are expected to be enrolled from different countries, including UK. Patients that miss samples may be ineligible for PK evaluation but will continue to receive INC280 and be included in safety analyses. Only patients with advanced solid tumours with cMET mutation/amplification/overexpression will be eligible. Patients are required to attend hospital for study assessments more frequently than normal during treatment; they will continue to receive INC280 while they give permission, their cancer is not growing and they tolerate INC280 without unacceptable side-effects.\nThis trial is sponsored by the pharmaceutical company Novartis.
REC name
North West - Greater Manchester South Research Ethics Committee
REC reference
16/NW/0805
Date of REC Opinion
28 Nov 2016
REC opinion
Further Information Favourable Opinion