Things are moving swiftly, at least for the present. I thought it would take many weeks to get near the Early Phase Clinical Trials Team but I had a call on Tuesday last asking if I’d like to attend a clinic on Wednesday. Naturally, I said ‘yes’.

There are databases of all current early phase trials and I did some looking-up, but I was a bit discouraged to find that there wasn’t much for  advanced metastatic colorectal cancer going on near me. After my doctor gave me the background info on what clinical trials were all about, I said as much to her. But although she agreed,  she also said there were trials at a more generic level that could be just as relevant for colorectal cancer as any other. This makes sense. Most of the specific-to-cancer-type trials are likely to be later stage (Phase II or Phase III), and the stuff of Phase I trials are newer targeted or biological therapies that should operate on most cancer types.

The deal is essentially that you get to take these newer drugs (which may have benefit) and they get to find out what are the maximum dosages before the side effects get too bad. The benefit we’re after is to stop or slow the growth of metastases, in other words to prevent the progression of the disease. Instead of your life expectancy curve dropping sharply to zero, the curve could get flattened out along a more gradual decline. It would be great to know how long this plateau typically lasts, but there just isn’t the data. Many studies get excited if the patient can become re-sectable (surgery) after treatment and then achieve a 5 year survival rate. But I had the surgery 5 years ago, so I already have that badge. You might then see another study that talks about a 10 year survival rate, but all that means is that the study took a more longitudinal view and not that the maximum expectation is 10 years. It could be just as likely to be 20 years, or 2 years.

They didn’t rule out future chemotherapy or radiotherapy for me, but the next line of treatment will be to try one of these targeted  therapies. There are many drugs in development, but most approaches fall into one of two categories. They either cut off the blood supply to the cancer cell so that it dies (Anti-angiogenesis therapy) by inhibiting the vascular endothelial growth factor (VEGF) protein produced by cells to create new blood vessels (angiogenesis); or the other way is to inhibit cell epidermal growth factor receptor (EGFR) receptors on the surface of the cell.  A “growth factor” is usually a protein or a steroid hormone which typically act as signalling molecules between cells. One example is the Hepatocyte Growth Factor (HGF) which activates a tyrosine kinase signaling cascade after binding to a specific receptor. A tyrosine kinase is an enzyme that provides an “on” / “off” switch in many cell growth functions. The Cetuximab drug is an example of a EGFR therapy.

Here’s a handy rule: if the drug name ends in “-mab” e.g. Cetuximab it is a monoclonal antibody, and if it ends in “-nib” e.g. Regorafenib it is a tyrosine-kinase inhibitor.

There are two specific trials they have in mind for me. The first possibility involves something called MP0250 which is a VEGF and HGF-targeting DARPin. A DARPin is a genetically-engineered protein that mimics the way antibodies work, which is highly specific protein binding to very specific targets.

The second possibility is a combo in which they will pair up two drugs called Vandetanib and Selumetinib. Vandetanib acts as a kinase inhibitor of a number of cell receptors, mainly the VEGF receptor, the EGFR, and the RET-tyrosine kinase. It was tried once before in conjunction with chemotherapy but the trial was unsuccessful. Selumetinib acts to block the MAPK kinase (MEK) protein, which is known to play a role in the growth of cancer cells that have a mutated BRAF gene.  If you recall, it had to be proven that I have wild-type (normal) KRAS gene before Cetuximab could be prescribed. It seems that Cetuximab has success in around 59% of cases which leaves over 40% where it does not work. If my new metastases appeared despite the Cetuximab, then I’d say it was not especially successful. Anyway, it is also possible that a mutated BRAF gene can be present and this *could* be responsible for the lack of success in the wild-type KRAS patients. I guess at some stage I’ll be tested for BRAF mutation.

That’s the science, and as I say it remains unclear which if any of these might be allowed to me. One thing that is clear is that I will have to commit to a hospital visit once per week as they will have to take copious measurements of me as part of the trial.