Use these databases to find a trial:

Clinical trials in the UK:

US and Worldwide clinical trials:

If you’re in the US you may be able to get access to new treatments via “Right to Try”:

Merk Patient Assistance Program:

Video transcript:

This is module 8 – all about clinical trials. It used to be, in the UK for example, only a few years ago, that ~1/2 of all cancer patients were in some trial. But that includes things like trials that are just about reducing side effects, or diagnostic trials, or screening trials etc.
What I’m going to mainly be talking about is trials for new treatments, and also combinations of treatments, which I think are the ones that are most relevant to us as cancer patients.

Before digging into the details, first of all I’m not a doctor and I’m not giving any medical advice. Secondly, please be aware of fake trials. Fake trials are things like clinics in Mexico and some parts of the US, offering weird and wonderful treatments where they say “this is a trial, but we don’t publish any data and it’s patient funded.” Basically, it seems they’re using loopholes in the law to get a lot of money for treatments. I know people have done those kinds of treatments that have claimed to get good results. I personally haven’t found any robust examples of people getting good results from that. I think you’d need a very good reason to join one of those trials.

Having said that, I was in a trial that was a patient-funded trial, because I needed access to a supplement. It was one where there was a lot of fuss about it ~ 5,6,7 years ago. Dichloroacetate is a standard lab chemical, and you can buy it online easily. But here in Japan, you couldn’t get a good, safe source that was guaranteed to be safe. The reason I wanted to take it was because I was having immunotherapy, and dichloroacetate with the type of immunotherapy I was having, potentially improved the results a bit. So I joined a patient-funded trial, sourcing very expensive dichloroacetate. It was expensive for me, because I had no money – it was several hundred $ a month for something you could buy online for $10. But the sources that we saw in Japan made it very clear they were selling it as a chemical, for use in laboratories. They said it was 99.99.% pure, but we cannot make any guarantee about what the 0.1% is, because it was made in factories for chemical production, not for human use. So you could get 0.1% arsenic or something too dangerous to take. So that’s why I was in this sketchy patient-funded trial.

A couple of really important terms: in trials you talk about the “end point” of the trial, which is the aim. Some cancer trials often use PFS – Progression Free Survival. That basically means that when patients in the trial start getting worse disease, especially tumor growth, they then basically leave the trial, and the trial is measured by the average progression free survival. It might say, in this trial, the average progression-free survival was 15 months. That means the people having this drug, after 15 months, the average patient had not got their cancer worse.

In the case of immunotherapy, this is not a good endpoint. The reason for that is, that with immunotherapy treatments, sometimes you get what’s called “pseudo-progression” where the disease looks like it’s got worse, the tumor is growing, and there’s even in cases of new tumors, yet the patients continue to do really well for an extended period of time. That’s why especially immunotherapy trials now, are often looking at “MOS – Median Overall Survival”.

Median is just one of the three averages that we use. Maybe you remember from school – the mean, median and mode. Mode is the most common number. Mean is all the numbers added up and divided by how many you had. Median is when you put them all in order and choose the middle value, and that’s good for clinical trials because you don’t want the number to be unfairly influenced by people who had to drop out of the trial, or those kind of outliers. You don’t want it to be unduly influenced by the incredible responders, who maybe for reasons completely unrelated to the drug, did really well. So the median is a good average for reducing the influence of the outliers.

In immunotherapy trials, you’ll often see that the end point is median overall survival.
You’ll see in cancer trials, comparing placebo with SOC (standard of care). In non-cancer trials, it’s quite usual to have people in the trial where they get placebo and no treatment, they’re literally just getting placebo. But in cancer drug trials, at least in the US, you can’t do a trial where the patient could potentially only get placebo. You can imagine a combination treatment, where they’re testing the addition of a drug to a chemo. The control group would get just the chemo plus a placebo, so that could be a sugar pill or a drip that is just a saline drip, and the standard care. The other group gets standard of care plus the drug that they’re testing. With cancer trials, you’re not going to have a situation where you’re just given a sugar pill.

The 3 main types of trial are : Open label – that’s where you know what drug you’re getting, you know you’re getting the drug, and the people doing the trial know you’re getting it.
Blind trials are ones where the patients don’t know if they’re in the placebo group or the drug group.
Double-blind are where the patients don’t know and neither do the clinical staff, so everything is done by barcode, and the clinical staff don’t know if you were in the group that got the drug or not.
Double-blind trials are considered the gold standard, but there’s obviously lots of situations with cancer treatments, especially non-drug treatments like radiotherapy or surgery, where you can’t possibly have a control group or it can’t possibly be blind, because you either have the surgery or you don’t.

With trials we talk about the phases. Phase1 trials, phase 2, phase 3 and phase 4. Phase 4 is a bit different, because that’s when the drug has been approved for use, so it’s sometimes called “post-marketing surveillance”. Phase 4 is of immense interest to cancer patients, because if we don’t get into a trial for whatever reason, we might still be able to access the drug as part of a phase 4 trial.

Typically with phase 1 trials, it’s a handful of people, maybe up to 20, but typically healthy people. The trial is just to see if the drug is safe. A big exception to that though, is trials with children, because children can only be in a clinical trial if they have the disease and can potentially benefit from the drug.
Phase 2 is looking at how best and safely to use the drug, and does it work.
In phase 3, you might have 300 -1000 people. In phase 2, you’re going to generally have up to 100, although I’ve seen phase 2 trials with a couple of hundred people.
In phase 3 for cancer trials, they’re often going to be multi-center trials, which means a bunch of clinics and hospitals in the country or internationally are part of the trial, and they’re all meant to be strictly following the trial protocol. When a trial is designed, there’s this protocol made, which is typically a 100 page document about how the trial is going to be done, how it’s going to be randomized, is it going to be a multi-arm trial.

Particularly for combinations of drugs which is typically how chemo is given, particularly for late stage patients, or molecular targeted drugs where they’re given with chemo, you might have a multi-arm trial, where you’ve got a control group, you’ve got another group that’s getting 3 drugs, and another group that’s getting two drugs. Multi-armed trials are really good because you get a lot of data in one go, which is good.

Another type of weird trial, which again is very relevant for cancer patients, are cohort trials where the trial is not really controlled – there’s not a proper control group. What they do is they give a whole bunch of people a treatment that they’ve got a good reason to believe works, and then to see if it works well or not, they essentially pair up each person in the trial with a similar kind of cancer patient, who has nothing to do with the trial. This is what’s called an external cohort group. Cohort trials are not great from a trial point of view, but there are many situations where that’s the best you can manage, because it’s very difficult to get a whole bunch of cancer patients with the same specific type of cancer, who have had the same treatments, especially for late stage cancer.

Those are the main types of trials. You’ve got open label, where everyone knows who’s getting what; you’ve got blind trials or some sort of blinded trials, where you as a patient don’t know if you’re getting the treatment or the placebo. Although I must stress that at least in the US and I presume other places, you can’t be just given the placebo with no treatment at all.

The gold standard of those, are double-blind trials where the people treating you, and you as a patient, have no idea if you’re getting the treatment or not. That’s because trial data often includes things that are a bit subjective. You get questionnaires about side effects etc, and of course if the doctor or oncologist or whoever the specialist is, if they’re asking you questions about side effects and they know that you’ve got the treatment, they might influence your answers subconsciously by the way they ask the questions.

As cancer patients, we can benefit from trials a lot. I should say that from the point of view of developing cancer drugs, cancer trials have not been fit for purpose. I think that should be very clear – that a big part of why cancer is so tough to deal with, is that cancer trials are just not very good. It’s hard to get into trials. There are selection criteria, which are inclusion criteria – reasons why you can be in the trial, and exclusion criteria- all the reasons why you get rejected.
For example, I had a genetic testing called MSK Impact, which is one of the two popular liquid biopsies on the market at the moment. The two famous ones are Foundation 1 Testing, and MSK Impact. I had this test and it showed 3 useful mutations – 2 of them matched up with trials that were happening in Japan. One trial I was recommended by the oncologist not to do, because she had treated a whole bunch of patients with one of the drugs and said the fatigue was horrific, so she advised me not to get in it.

The other trial I was rejected, because it was a combination drug trial, and I had had one of the drugs already. That’s a very common situation if you’re a late stage cancer patient and you’ve been through a lot of drugs – you’re often going to be rejected because you’ve had a drug in the combination, or the related drug.
Unfortunately if you’re trying to get into trials at an early stage, then you often don’t meet the inclusion criteria, because a lot of trials are aimed at patients where the treatments have failed. Although the medical people for some reason always use this phrase: “the patient failed the treatment”, clearly it’s the treatment that failed the patient.

So what use are trials to us? Well obviously if you can get into a trial, that’s very good. I did when I had that MSK Impact test which was a few years ago, when it was ~$10,000. I did that as part of a trial, so I didn’t pay for the test. The University Hospital where I was at paid for the test. They were doing a trial to see if liquid biopsy was useful for patients in Japan to make treatment decisions. The university paid for a whole bunch of patients in Japan to send off blood samples to the US, to Memorial Sloan Kettering University Hospital, and we all got our data back. I’m glad I didn’t pay $10,000 for it, and it’s nice to have a full genetic sequence of my cancer.

Trials are good if you can get into them, but if you can’t get into them, then you can still benefit a lot. One more point that I should have mentioned about the placebo in trials – cancer patients often say, “What’s the point of being in a trial, as I might be put in the placebo group?”. In every trial, if the drug works really well, all the patients in the placebo group are then given the drug, if it’s safe to do so. This is called a crossover. Some trials are actually designed as crossover trials from the beginning, where basically the people in the placebo group get the placebo for a certain period of time, and then they become part of the treatment group anyway.
If the trial goes really well and you happen to be in the placebo group, and the people in the treatment group are getting vanishing tumors etc, then you’re going to be moved over to the placebo group anyway, because there’s an ethical consideration.

To some extent, maybe we could choose treatments based on trial data. I generally found that more useful in the negative, as in, my oncologist is recommending some treatment and I point out that the trial data for that is poor because it was a handful of people, 10 years ago. I found it’s going to be useful when I am discussing treatment options with my oncologist.

A much better use of trials, if you’re not in the trial, is using it to find out about new treatments and then accessing those treatments without being in the trial. One of the big secrets in the cancer community, for want of a better word, is that as a patient, you can contact a drug company and ask for some drugs. This is a really useful way where you can make use of a trial. So if you see a phase 3 trial happening, or particularly if you see a phase 3 trial from a few years ago that’s no longer recruiting, you can contact the drug company and try and get hold of that drug. The same if it’s been very recently approved, and you can’t get it because maybe it’s not approved in your healthcare system, or maybe it’s approved but your insurance company doesn’t want to pay for this. Then you can contact the drug company directly. This is often called “compassionate care” or “compassionate drug provision”.

For example, the drug company Merck has something called a “Patient Assistance Program”, that’s set up to give people free access to drugs. You can go on their website which is (I’ll link to that from my site as well), you can search for drugs that you’d like, and you can contact them and try and get them for free. You can also contact a teaching hospital or University Hospital where you are, and see if they can access the drug for you as a case study, e.g. a one-patient case study.
I’m not sure about outside of Japan, but in Japan you can do this but it’s slow, because typically they’ll have to go to the Ethics Committee, and in Japan it’s super-bureaucratic. Hopefully wherever you are, things are much quicker. So you can access trial drugs sometimes as a case study.

For contacting drug companies, generally you just go to the website and look for things like Patient Liaison Services or Patient Assistance. If you can’t find that, the people to really contact are public relations, because they’re the best informed about stuff happening in the drug company. They’re always publicizing the trials. So going through the public relations department is a good way to get contact.

Nobody likes to hear this, but physical mail works much better than email, although having said that, at least with email you can spend 30 minutes in contact with a whole bunch of different drug companies in one go. But physical mail is always really helpful.
Another thing you can do is use LinkedIn, because on LinkedIn, we can see lots of people working for drug companies. You can make a free account on LinkedIn and then you can search on LinkedIn. If you log into LinkedIn but then search on Google (you searched on Google when you’re logged into LinkedIn) for Merck, then on LinkedIn you’ll find a whole load of Merk staff or Glaxosmithkline or whatever the drug company is, on LinkedIn so you can just contact people directly. Be polite, don’t hassle people. But we’re dealing with very serious stuff here, so it’s worth contacting people directly and in most cases, they’re just going to refer to someone else in the company. But at least you can then say to the PR people or the patient assistant people, “Such and such a person at Merck said I should contact you about getting access to this drug”, which is a lot better than a completely cold contact.

I think that is a reasonable brief introduction to trials and I hope it’s been useful. As always, more parts of this course are coming soon.