Cancer Research UK to Test Targeted Drug in Pancreatic Cancer

A dual kinase inhibitor* is entering a clinical trial for advanced pancreatic cancer in combination with gemcitabine as part of Cancer Research UK’s Combinations Alliance.

The PAGoDA** trial aims to explore the effect of this drug on advanced cancers and will be conducted through the Experimental Cancer Medicine Centre (ECMC) network, supported by Cancer Research UK and the UK Health Departments. Led by the Manchester ECMC and sponsored by the University of Glasgow Clinical Trials Unit, the trial will span four sites across the UK, with the first patients expected to start treatment in early June.

The novel combination of drugs targets the process of nerve invasion, observed in over 80% of pancreatic ductal adenocarcinoma (PDAC) and is associated with tumour spread and severe pain.
The study will use PLX7486 to target Trk kinases, which are believed to help cancer cells invade nerves. It’s hoped that PLX7486, in combination with the chemotherapy drug gemcitabine, could improve progression-free survival and reduce pain for pancreatic cancer patients.
Once a safe dose has been determined, clinicians will assess if the combination is able to control pain for patients and whether it has an effect on tumour growth. It’s hoped biopsies from a subset of patients will also shed light on how the drugs affect the development of both nerves and the tumours themselves.
Dr Natalie Cook, chief investigator of the trial and clinical lead of the Manchester ECMC, said: “There is still a lack of options for pancreatic cancer patients and survival remains stubbornly low. Some patients experience pain that is very difficult to control, and we know that these patients tend to do worse than those with controlled symptoms.
“Preclinical models show that giving this drug combination seems effective at stopping the cancer cells growing and multiplying. Hopefully, this will translate into clinical benefits and enable us to better control the pain and spread of cancer in patients.”
Cancer Research UK is committed to funding more research into hard to treat cancers such as pancreatic cancer. Only 1% of people diagnosed with pancreatic cancer in England and Wales survive their disease for ten years or more, and the treatments currently available cause significant pain as a side-effect.
Dr Ian Walker, Cancer Research UK’s director of clinical research, said: “Through our Experimental Cancer Medicine Centre network, this trial will bring together doctors and researchers to get the most comprehensive picture of how a new treatment combination targets pancreatic cancer. Close collaboration like this enables translational research - progressing new drugs from the lab to improving the lives of patients in the clinic.”
* Plexxikon Inc. will provide PLX7486, a selective dual Trk/Fms Kinase Inhibitor.
** PLX7486 And Gemcitabine in patients with metastatic pancreatic Ductal Adenocarcinoma. The Phase Ib trial will initially establish the safety and tolerability profile of PLX-7486 in combination with gemcitabine, and conduct a preliminary assessment of the drug combination’s efficacy on tumour-related pain in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC).

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