Phase 1B study of Axitinib plus Crizotinib in advanced solid tumours
Research type
Research Study
Full title
A phase 1B, open label, dose escalation study to evaluate safety, pharmacokinetics and pharmacodynamics of axitinib (AG-013736) in combination with crizotinib (PF-02341066) in patients with advanced solid tumours.
IRAS ID
181538
Contact name
James Larkin
Contact email
Sponsor organisation
Pfizer Inc., 235 East 42nd Street, New York, NY 10017
Eudract number
2015-001724-31
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
IND 63,662 , US IND; IND 73,544, US IND
Duration of Study in the UK
1 years, 5 months, 15 days
Research summary
Renal cell carcinoma (RCC) is the most common type of kidney cancer. Current therapies focus on targeting vascular endothelial growth factor (VEGF) signalling pathways, which have been implicated in the production of blood vessels by the renal cancer cells, thereby enabling the cancer to grow. Despite the success of these therapies, the majority of patients ultimately develop resistance to such regimens, one of the reasons being the overexpression of the mesenchymal-epithelial transition factor (c-MET), which also leads to cancer growth.
Therefore, it is proposed that combining inhibitors of both the VEGF and c-MET pathways may provide durable clinical benefit compared to treatment with a VEGF therapy alone. Axitinib (INLYTA®) is a VEGF inhibitor approved for the treatment of advanced RCC after failure of one previous treatment. Crizotinib (XALKORI®) is a c-MET inhibitor approved to treat a type of advanced lung cancer.
Pfizer Inc. is sponsoring a study to collect information about the safety and effect of the combination of axitinib and crizotinib on different types of solid cancer and to find the best combination dose for patients with RCC.
This study will be conducted in two phases:-
1. A dose escalation phase, to explore the oral administration of axitinib plus crizotinib on a continuous schedule and to determine the best combination dose. About 25 participants with different types of advanced solid cancers will take part.
2. A dose expansion phase, to assess the safety, tolerability and anti-cancer activities of the combination of axitinib with crizotinib in participants with advanced RCC. This phase will consist of two cohorts of ~20 participants each (cohort 1: no prior systemic therapy; cohort 2: 1–2 prior systemic therapies).The study is being conducted in the US and the UK at approximately 10 research sites. The dose escalation phase is currently ongoing in the US. In the UK, participants will be recruited for the dose expansion phase only.
REC name
North West - Haydock Research Ethics Committee
REC reference
15/NW/0627
Date of REC Opinion
20 Aug 2015
REC opinion
Favourable Opinion