DK37's Personal BIG PICTURE Opinions on CLINICAL TRIALS

[DK37]

This is something I believe strongly in - so I'm cross-posting it across my multiple social media outlets:

Here is a personal opinion CLINICAL TRIALS 101 post from my >20 years of being an oncology drug discovery scientist – intentionally just focused on the “big picture” questions.

When should one start "thinking about" clinical trials?

I believe you should start *monitoring* clinical trials immediately after receiving a currently incurable Stage IV diagnosis (if you want to be especially proactive even sooner). Note there is a difference between monitoring and applying… but once you hear that currently incurable diagnosis, you know in your treatment plan that chemo will only work for so long. How long? Depends on the patient… Could be 8 months, could be 8 years – but the point is that when your chemo options start dwindling (at the latest), you want to already have an idea of what is out there and some trial options in mind. Trials take a while to set up logistically and it is better to not have to be trying to figure them out in a panicked/rushed situation. Also: if there is a scientific breakthrough – you want to know about it in order to consider switching over sooner, rather than later!

When should one consider *applying* for clinical trials?

That is a very patient specific, personal medical decision. In general patients (for logical reason) are applying earlier and earlier than they used to. The reason? Immunotherapies and their “potential” – they changed everything. Back in the days when a clinical trial was looking at a “new chemo” there really wasn’t an incentive or logical reason to doing a clinical trial before all standard of care chemo options were exhausted. Why try an unproven chemo when you could just do a proven chemo instead? NOW… the world is completely different. Now you are not comparing two chemos – now you are comparing a known chemo with an experimental agent with “the chance” of VERY durable long term response. Maybe only a low chance, but a real CHANCE. In fact, you DON’T want to wait too long to apply for a clinical trial because your body will be weaker which logically may decrease the odds of an immunotherapy from working and in fact… trials will not take you if you are too weak or have too advanced disease/poor health. When you hear oncologists talk about waiting until you exhaust all options, they are obviously very old fashioned and have not kept up with recent clinical trials. Clinical trial design actually reflects this – although most trials require you be resistant to at least one form of standard of care chemo (e.g. FOLFOX) it often is only 1-2 lines, nowhere close to all lines chemo needing to be exhausted. We even have a few immunotherapy trials which do not require resistance to any standard of care chemo prior to trial.

Are there immunotherapy trials for MSS-CRC?

When you hear an oncologist say that “immunotherapy doesn’t work for MSS-CRC” or that “there are no trials”. In the first case they are only referring to the fact that there are no FDA approved immunotherapies for MSS-CRC. There have been immunotherapy responses in MSS-CRC. Yes, MSS-CRC is in fact tough to treat with immunotherapies but for the people it has worked in so far, I am guessing that they were probably glad they tried... In terms of no trials being available for MSS-CRC patient enrollment – this is factually false. I have been maintaining a curated list of immunotherapy trials that are open to MSS-CRC patient enrollment for over a year now (it started out as my personal list --- stay tuned for a PENDING ANNOUNCEMENT). Are there immunotherapy trials open to MSS-CRC patients? I have a list of over 50 of them!

Will most clinical trials fail?

Yes. Most fail. But my personal opinion (being currently incurable Stage IV MSS-CRC myself): I would rather do trial(s) and try for that small chance versus simply accepting where standard of care chemo ends. We all know where it ends. In contrast, I think I would rather take a chance on a trial, even if its chances are low, like Sleen did (as you all read about in the NY Times a few weeks ago) or as StephenWinsToday did in our MSI-high CRC population.

You’re free to agree or disagree... but those are my “big picture” thoughts and personal opinions based upon a lot of years in drug discovery research (and being a currently incurable MSS-CRC patient myself).

No matter what path you decide to follow, wishing you all the best, -DK37

[Maia]

Thank you, thank you, thank you. Thank you.
Hope this is read repeatedly, carefully, for many, for those here, for others just surfing the web.
Be well, Tom!

[Brikee]

Thank you for sharing this. Look forward to your personal list of immuno trials!

[jortego128]

Agree Tom, and I would just like to add-- certain trials require a high ECOG status-- sticking with chemo till it fails may even render you UNABLE to participate in a trial.

We went the chemo route for about 8 months-- according to the radiologist and onc, met stability was acheived, but moms physical condition continued to worsen, something didnt add up. By the time of our appointment in January at MDA, which I began trying to schedule at the end of November, the oncologist was shocked that she was still being given chemo in her physical condition.

Despite being on this board almost daily since her dx, I failed to recognize SIRT as an option and that it could be done for CC liver mets outside of trials and so close to home. Once I realized it, I scrambled for an appointment, it was too late.

Have you started your protocol yet? I hope all is well.

[bitchslapped]

I would wager to guess that a lot of people do not realize that those papers signed @ their initial oncological visit for chemotherapy @ Stage IV dx read for palliative treatment. There is some thought "out there" that clinical trials s/b considered @ each decision-making point in treatment. Enrollment in clinical trials is a fraction of what it could be. Do not wait for your oncologist to address it. Oncologists deliver chemo. Be your own advocate.

There are "sticky threads" @ the top of the board w/trial finders included for those that need help that will search for you & notify you when trials come up for which you may qualify. There is online & phone support. A link to the ECOG status is also included on that thread. There is such a thing as becoming too weak to participate depending on the trial.

viewtopic.php?f=1&t=53238

One thing to bear in mind is that once you have tried immunotherapy, it may preclude you from other immunotherapy trials. Perhaps that s/b clarified by someone more knowledgeable than me.

It appears to be especially important for our "under 50 crowd" where cancer seems most aggressive & difficult to treat w/standard of care therapies.

Great post DK.
BS

[Maia]

One thing to bear in mind is that once you have tried immunotherapy, it may preclude you from other immunotherapy trials.

It's not like in the old days --that happens less and less: that a previous immuno trial precludes from going for other . THAT's why there is a column on that trial finder/curated spreadsheet that simply reads "Allows prior PD-1" --yes or not. It means if that particular trial admits patients who already got a previous treatment (usually, a trial) with a checkpoint inhibitor.
I know patients who are into their 2nd, 3 rd or even 4th trial by now, and some of those were immunotherapy.
I'm not saying that it is not difficult to find a match for a trial, for many reasons (starting with location, sometimes); BUT the times are changing, since a couple of years ago; it is already a new world for those MSI-H and this year it is reaching MSS patients (the majority), hopefully. We only keep doing our best, each one in their humble or not so humble way.

[vilca11]

I am not sure, if I should be posting my thoughts about clinical trials after all my favorite people posted their extremely positive attitude to them. But then, if no one has a different opinion, people who are not as well informed as our "oldest" members, might see clinical trials as an option that should be pursued, no matter what time, pain, suffering and terrible complications, including death, it involves. Time is an essence for stage 4 fellows, unfortunately... Too many deaths in clinical trials and after them too, unfortunately... Too many life threatening complications, unfortunately... There are articles on internet with headings something like "truth about clinical trials" - everyone should read them before making their choice...

So, if time is an essence for us, stage 4 patients, we have to think also how we would like to spend that time after all other tortures we have been thru already.... Yes, thanks God Sleen is well, but how many people on our board went into trials without results and are dead now? And how many are well? 2? Who spent their time better - Frenchie or Karen, who also were on TIL's with Sleen? I am categorically against chemo for life protocols, but for some people, like BB, it works - again, very rare occasion, and I think, it is mostly thanks to his bike mileage and surprising compatibility with his chemo. With clinical trials I am not so much against participating in them, but just want people to realize the real picture - as Tom mentioned, the chances are very low, I would say miserable, not low...Do not go far, just look - Sleen was the only one succeeded with MSS-CRC, and it was such a huge deal that it was posted in NY Times or wherever, I did not read that article, since I know the story....

Another thing is doing trials for the humanity benefits - yes, if you want to benefit humanity this way, it's a go. And many people do them for this reason, God Bless them... But going into trial without realizing your real chances (close to zero) and knowing the results of all the trials designed for MSS/CRC in the past 3-4 years - no results in any of them, but this one case with Sleen - seems to me really disrespectful to the time you have left on this Earth.... I know, I will be crucified here for my opinion, but it is just my opinion and may be it will make people, who place too much hope in clinical trials, to think twice before enrolling...

Sorry, guys, just do not kill me for all the above
Hugs, Vilca

[jortego128]

^^
No worries Vilca, your honesty is refreshing and welcome. If one really wants the best QOL, and can accept their days are numbered, perhaps they would forego standard protocol chemo as well. There are people that do. I truly believe in my heart that my mother endured unnecessary suffering by taking FOLFOX and FOLFIRI. 9.3 months from dx? She would have had better QOL and likely lived just as long had she not done it at all.

I was in fact told by my family doc that she should consider NOT taking chemo-- my initial reaction was shock and anger that he would suggest such a thing....now, looking back, I can see where he was coming from. The chemo, at least in her case, did nothing but cause unnecessary suffering.

Personally I still believe in a blitzkreig attack style aggressive approach to treatment-- however, I also believe and understand that "standard of care" chemo may not always necessarily be included in that approach. Surgery, HAI, SIRT, immunotherapy, and trials should all be considered in the most aggressive manner from the start. I firmly believe that had my mom gotten SIRT in the very beginning, she would have lived longer than she did. Maybe its not healthy to think that way, as hindsight is always 20/20, but I do anyway.

[bitchslapped]

I loves me some Vilca! No one will argue that it is a personal decision depending on one's history, the road they have traveled. We don't have to look much further than our "In Memorium" sticky thread to remind us of therapies to date. QoL matters however one defines it for themselves, but we don't always have control over that either. The younger ones, particularly under 40 seems to be increasing w/resistance to standard of care chemo w/more aggressive spread. The immune system is so powerful it can either protect us or turn on itself. Think of how many other diseases could be cured if science could find the secret to the immune system.

Clinical trials are just that. Not to say there are not some possible conflicts of interest too, considering Big Pharma sponsors most of them, however TIL @ NIH is government run trial. Also, transparency in reporting has been lacking in clinical trials. I w/b interested to know if any better stats are published since a couple of years ago.

For some clinical trials are a chance, an opportunity for hope. So clinical trials may be another tool in the arsenal...or... unfortunately it may be their only tool.

BS

[MissMolly]

Vilca:
As someone myself who is on my final-leg of my life, I agree with your sentiments and opinions.

I have endured frail and fragile health for over 20 years, a slow and agonizing loss of health and well-being. Without health, the foundation of life is eroded. Work and hobbies, friendships and relationships, going to a movie or a cafe for coffee . . . all become tenuous. I have not been to a restaurant to share a meal with family/friends in years. My life has become more and more narrowed and insular. Going out for a car ride has become a major celebration.

For those who are not accustomed to the total-body experience of being unwell and in un-mitigating pain, the lens of extending one's life may be an all-out focused goal.

I speak for myself here. A life in constant pain, as mine is, is a life of few joys. A life where one is limited in being able to get up and walk to the bathroom, is a small life. I have a baseline of life quality that is essential to me.

The many costs associated with my care, despite excellent health insurance, are staggering. I would rather be spending my money on something that would bring me some modicum of pleasure or joy. But that is not to be the case. My financial savings, accumulated through years of working diligently in a career, are dwindling. Healthcare costs are astronomical. For all that I have spent out-of-pocket on hoped for treatments and procedures, I have little personal benefit to show. My body has continued to decline while discomforting symptoms have continued to grown.

I read a recent article that ranks United States' healthcare in 11th place of the 11 industrial nations. The United States has the highest health care expenditures per capita among the 11 industrial nations . . . and has the lowest measures in terms of access to health care, quality of care, and overall efficacy. For all the misguided and poor care that I have received, I would agree with the poor assessment of healthcare in the US.

I have had a prior near-death experience. It was a profound and life-changing experience. I do not hear death as much as I fear unrelenting pain and loss of physical and cognitive independence.

I am not giving up in deciding to be on hospice. The phrase "giving up" has negative connotations that I take exception to.

My body is tired. I am ending my personal life's race on my own terms.
- Karen -

[DK37]

Hi Vilca,

As a response to your comment, I just wanted to start out by saying thank you for posting it. It is a very valid viewpoint... participation is clinical trials is a very personal decision based upon not only medical situation but also personality, life situation etc. Clinical trials are NOT for everyone.

People sometimes ask me "my personal thoughts" on my participation in trials. So these are my thoughts as patient (i.e. taking into account what I said above and closer in thinking to your comment than you might expect).

- Before I would even "consider" a trial that would make a HUGE impact on my family life (i.e. flying cross-country for the trial site) - the trial would have to have shown significant activity in at least one MSS-CRC patient. Most trials fail and do not show that. Without that data in hand (and I include anecdotal accounts of objective response to treatment, not just publications) - I personally would not severely disrupt my family life which may be in its waning days --- for a trial with zero signs of clinical success yet - because... the vast majority of trials fail.

- An exception: If there is an unproven BUT SCIENTIFICALLY VALID trial WITHIN DRIVING DISTANCE of my home - I will consider those. Because I can take that high risk of failure but high potential upside benefit (LIFE!) without severely disrupting being around the house with me kids etc.... That was actually a key part of my decision process when I applied for my current trial (NCT02636036 - dosing in Feb (delayed due to current palliative radiotherapy treatment for pain)) - it opened up a trial site within driving distance of me!! (and I love the mechanism of action/science - AND they were OK with my melanoma diagnosis!)

So those are my own patient personal decision points on how to balance "going for the lottery ticket dose response of an immunotherapy trial" with potentially end of life family-time quality of life. Everyone will come out differently on that spectrum of balancing those two factors, that is where I ended up for me!

Cheers,

-DK

[vilca11]

Ditto, Tom... I had no doubts that your decision is well thought thru... And God is a witness how much I hold fingers for you, our incredible wonderful Tom!
Stella