New precision medicine study for patients with cancer in the biliary tract

A new study at UCLH and UCL aims to extend survival for some patients with cancer in the biliary tract by treating them with therapies specifically tailored to the genetic profile of their tumour.

Patients diagnosed with the three main types of bile duct cancer (intrahepatic, perihilar or distal cholangiocarcinoma) or with cancer of the gallbladder may be eligible for participation in the SAFIR-ABC10 trial. They will have their tumours genetically profiled and will then be offered one or more of seven different anti-cancer therapies best matched to their tumour profile.

Bile duct cancer is also called cholangiocarcinoma. It is a type of cancer that starts in the bile ducts, small tubes that connect the liver and gallbladder to the small bowel. They carry a fluid called bile. This helps to break down fat from the food we eat making it easier to digest.

UCLH consultant medical oncologist and UCL Cancer Institute clinical researcher, Professor John Bridgewater, said: “These cancers are becoming more common. With the current standard of care, patients typically only live for one year after treatment begins. So it has become increasingly more urgent for us to try to identify more innovative and effective alternative treatment options.”

Standard treatment for advanced biliary tract cancer is based on chemotherapy, and more recently, supplemental immune therapy.

But this international study – led by the French hospital network Unicancer, with chief investigator Dr David Malka, medical oncologist at the Institut Mutualiste Montsouris in Paris – aims to recruit some 800 participants from all over the world and offer them therapies tailored to the genetic make-up of their tumour.

Prof Bridgewater is leading the UK arm of the trial which is sponsored by UCL and run through the Cancer Research UK (CRUK) and UCL Cancer Trials Centre, as well as UCLH.

He said: “This is the first precision medicine study for patients with cancer in the biliary tract and the first time this patient group will be offered these anti-cancer therapies.

“Genomic profiling of patients has been possible for some time but, in the past, there was little we could do with the results of this profiling. The SAFIR ABC10 study resolves this problem by providing seven different therapies which we can match up with the specific ‘targets’ found in each patient’s tumour.”

Dr Tayyaba Jiwani, science engagement manager at Cancer Research UK, commented: "The outlook for people with biliary tract cancers is often poor, because they are typically diagnosed late with few treatment options other than chemotherapy.

“There is a pressing need for new treatment avenues and through SAFIR ABC-10, we’re proud to support one of the first precision medicine trials for biliary tract cancers. With trials like SAFIR ABC-10, we’re accelerating the development of more personalised, genetically targeted treatments that are more likely to be effective against cancer, so that more people can live longer, better lives free from the fear of this disease.”

Helen Morement, CEO of AMMF – The Cholangiocarcinoma Charity, commented: “After many years of very few therapies for those diagnosed with an inoperable cholangiocarcinoma, there have been some notable advances recently. Importantly, the inclusion of the immunotherapy durvalumab to the long-established standard of care first line chemotherapy combination gemcitabine and cisplatin, and the recent introduction of molecular (genomic) profiling which enables the identification of targets in the patient’s tumour which can be addressed by specific therapies. Excitingly, SAFIR ABC-10 is a first line study which harnesses both of these advances.” 

Prof Bridgewater is also supported by the National Institute for Health and Care Research (NIHR) UCLH Biomedical Research Centre.

For UK participants, genetic screening will be carried out by the NHS North Thames Genomic Laboratory Hub.

The trial also involves digestive oncology groups called the National Cancer Research Institute Upper GI Group (UK), PRODIGE (France) and the Belgian Group of Digestive Oncology (Belgium).

Note: The seven anti-cancer therapies offered as part of the study are futibatinib, ivosidenib, zanidatamab, trastuzumab, neratinib, encorafenib and binimetinib. These therapies will be offered – alone or in combination – to patients whose tumours carry genetic alterations at the following sites: FGFR2 (fusions/rearrangements, mutations), IDH1 (mutations) HER2 (amplifications, mutations), BRAF (V600E mutation). For patients whose tumours do not have these genetic alterations, other studies are in development, which will become part of the SAFIR-ABC10 trial in the next 12 months.

Participant’s tumour shrinks to half its size

One of the participants on the trial is Ronald Glover, 76, of Chislehurst. He said:

“I was diagnosed while seeing a urologist with some symptoms of a different nature. A scan revealed a tumour on my liver so I was subsequently transferred to the liver team. 

“They suggested surgery to remove the tumour, but the first attempt had to be abandoned because I went into anaphylactic shock and the second attempt, about a month later, was also abandoned because the surgeon felt that the disease had spread.

“At that point I was told I could expect to live for another seven to 12 months. It came as quite a shock.

“Fortunately, my daughter, who was at the appointment with me, asked the surgeon what she would do if a member of her family was given this news, and she said she would try to get in touch with Professor John Bridgewater.

“That’s what led us to Professor Bridgewater and UCLH, when we learnt about this new clinical trial. I was recruited in July this year, a very willing participant. I had four three-week cycles of chemotherapy and immunotherapy (durvalumab in combination with gemcitabine and cisplatin) in the first phase, and I had no side effects at all. I had been warned that I may have some reaction to the treatment but I was absolutely fine. At this point a scan showed the tumour had reduced in size by 36%.

“A blood test helped identify the gene that was the cause of my cancer and I entered the second phase of treatment around mid-October. I was prescribed 20 weeks of a targeted cancer therapy drug called ivosidenib. After about six weeks, I had another CT scan which found that my tumour had shrunk down to 30mm, now almost 50% down from the initial measurement.

“I am now eight months down the line, fit and well, and whatever Professor Bridgewater is doing is working really well for me. I feel really grateful, and privileged to have been given the opportunity to be a part of this trial.”