Meeting with CRUK re BILCAP

At the meeting with CRUK on Wednesday 21st September, to discuss the proposal that AMMF financially support the ongoing BILCAP trial, one point that came across very clearly was the painstaking care which which trials are organised and conducted and how everyone wants results as quickly as possible.  However, in order for outcomes to be credible and dependable, results must be meticulously gathered and analysed and that, throughout any trial, the patient’s quality of life is always uppermost in everyone’s minds.

During the meeting various questions were raised and, in each case, the CRUK representatives answered them as fully as possible.  Where they didn’t have answers, they promised to find out.

A quick resume of the BILCAP trial – This trial is comparing surgery followed by capecitabine treatment with surgery alone for cholangiocarcinoma or gallbladder carcinoma.  The trial is building on experience from other studies in an attempt to give robust, practice-changing evidence for the effectiveness of using chemotherapy after surgery.
(As referred to below in the text – the BILCAP research team have recently presented their work at ASCO, and their very informative poster giving all details on this trial to date has now been given to us – pdf available below.)

Q.  Why is capecitabine the chemo of choice for the BILCAP trial?

A.  Previous studies have shown that cholangiocarcinoma can be sensitive to chemotherapy.  A number of small studies in people who have undergone surgical resection suggest that the drug 5-fluorouracil (5-FU) may be helpful in prolonging survival from cc.  Leading on from there, capecitabine, which is an oral form of 5-FU, is now being used in a far larger study, BILCAP, which it is hoped will give the conclusive proof required to change clinical practice.  (This pill form of 5-FU chemotherapy means that patients can take the treatment at home, avoiding the need for hospital visits, which is an important consideration in terms of quality of life.)

Q.  What happens if a patient’s cc recurs whilst on the BILCAP trial?

A.  They will be offered “treatment as indicated”.  On further questioning as to what this meant, it would seem that if the patient’s consultant felt there was another treatment that would be helpful, then that would be offered.

Q.  This is a lengthy trial – will there be interim results?

A.  The primary aim of this large trial, involving 360 people who have had sugery for biliary tract cancer, is to see if capecitabine will extend survival compared to surgery alone – the effect of the treatment on the percentage of people surviving for five years or more after their diagnosis, and on the length of time before the cancer returns.  If they can show that the drug treatment has a positive effect on any of these, it could lead to a change in the way cc patients are treated here in the UK and internationally.
The trial has been running for several years, with 234 people enrolled to date.  All patients will be followed up for up to 5 years, so it may be some years until the final results are known.  Although everyone wants to know the results, and there are some interim results available, it is considered very important that the final results are known before the true effects of the drug treatment can be fully interpreted, and so its impact can be understood.
The BILCAP research team recently made a presentation at the 2011 ASCO conference (The American Society of Clinical Oncology) – a link to a pdf of their informative ‘poster’ is below – reporting that recruitment for the trial is going very well.  A small interim analysis of survival and toxicity data was also presented.  The survival analysis was performed at a very early stage and doesn’t really give any indication of what will happen in the longer term.

Update 07.10.11

What is the longest length of time a patient has been on the trial? There are patients who have now been followed up for five years.

Q.  What are the toleration/toxicity levels of this trial?

A.  As reported at the ASCO conference, the side effects of the treatment were mainly as anticipated and of a low grade – hand/foot and GI toxicities being the most prevalent – meaning they could be dealt with easily.  (The patients are asked to complete a form after each round of treatment, and the percentages of the various areas of side effects can be seen on the poster.)

Q.  Have many people withdrawn from the trial?

A.  The CRUK representatives couldn’t answer that, but promised to find out.

Update 07.10.11 – 

What is the number of people removed from the active side – because it has been intolerable?   They are unable to supply this information, but re-iterated that the side effect profile suggests that the treatment is very well tolerated.

We did talk about the ABC-03 trial – and, briefly, this is the information we now have on it:

Most biliary tract cancers are inoperable, mainly because they are diagnosed at an advanced stage.  In a previous sudy, ABC-02, the combination of cisplatin and gemcitabine was shown to give extended survival in patients with advanced, inoperable cc over gemcitabine alone.  However, to try to improve outcomes even further, the ABC-03 trial has been set up with a further drug added to the combination – cediranib.

Cediranib is an “anti-angiogenic” drug.  This type of drug works to prevent cancers from driving the growth of new blood vessels to provide the high levels of oxygen and nutrients they need.  Cholangicarcinomas usually build up a dense network of blood vessels around themselves, so it is thought that cediranib could be a useful addition to the armoury.
If the results from this trial are positive, plans are that a larger trial would be developed.