My Very Own City of Hope: MSS-CRC Clinical Trial #1
As long time readers of my blog know – I have been in a quandary since I was diagnosed with (presumably cured) Stage 1 melanoma in January 2015. That diagnosis, even though presumably cured by simple day surgery, with zero signs of recurrence ever since e.g. by monitoring with blood liquid biopsy, effectively blocked me from most colorectal cancer (CRC) clinical trials.
Without clinical trials there is statistically an essentially 100% chance I will die of CRC in my 40’s. I personally find that notion unacceptable.
This blockage from clinical trials was the height of irony (haha Universe – funny one!) since I am a cancer drug discovery scientist and clinical trial education of fellow patients is my passionate advocacy soap box issue. My first stab at an immunotherapy clinical trial in February, 2015 was literally taken out of my hands as I was about to sign consent paperwork when my melanoma history was noticed.
So my (presumably cured) melanoma was a real problem… it blocked me from most CRC clinical trials listed in clinicaltrials.gov – even ones I was scientifically advocating fellow patients to discuss with their MD’s.
Backing up the story a bit…
I am friends with a Professor of T-Cell Immunology – a brilliant guy and a fine human being too. A powerful combination to have as a friend & scientific advisor! We were meeting to discuss clinical trials and he brought up a trial NCT02636036 “Phase I Study of Enadenotucirev and PD-1 Inhibitor in Subjects With Metastatic or Advanced Epithelial Tumors (SPICE)”. I told him I loved the trial and had been monitoring it for months but… they clearly excluded people with secondary cancers like my melanoma.
My friend was insistent – he told me to double-check the exclusion criteria.
I had double-checked the criteria off and on for months so I didn’t see the point. I nodded politely. But… when I left his office, he had been so insistent (and it is such a cool trial), when I got back to my office, I pulled open the trial’s webpage on my computer.
The melanoma exclusion criteria was nowhere to be seen. I rubbed my eyes and looked again. Gone. I carefully looked through the exclusion criteria a third time with a fine tooth comb.
It was gone. The date stamp on the clinicaltrials.gov record said it has been updated about 2 weeks prior. I had no idea it had been updated and wouldn’t have known without my friend’s insistent pushing to double-check. This yet again illustrates the power of lucky breaks in the high stakes world of currently incurable cancer as mentioned by the recent STAT News article on my cancer journey. If my friend hadn’t pushed me on the exact day he did… the rest of the blog post would never have existed.
The trial was listed as “Not Yet Recruiting” in California (2 sites in LA) but one thing I had also just recently observed and learned from a different friend – in the experimental therapy world, you have got to be aggressively proactive since you are not following standard protocols. So with that fresh example in my mind, aggressively proactive I was.
First I emailed the trial’s contact info that very same day. Then my oncologist contacted them. No definitive answers. At this point, thinking back to my friend’s aggressive proactivity – I changed course. I knew the names of the oncologists running the two LA trial sites – but not their contact info. One email I found from a medical paper he wrote. The other was not found that way – but… I could find via google how his hospital’s email system systematically converted names into email addresses. A few minutes of detective work allowed me to have his email address figured out. 🙂 I immediately emailed both doctors explaining to them my strong interest in the trial. Gratefully they both answered immediately.
I made an appointment at the earliest possible date between the two – which turned out to be at the very well regarded City of Hope Medical Center in Duarte, California – in the LA metropolitan area. I talk a lot about Hope… it seemed like a very appropriate place for me to have my first clinical trial 🙂
The appointment was yesterday. It went very well – I have been accepted into the trial!!
So what exactly is the trial?
The trial is a combination trial specifically recruiting for MSS-CRC that combines an oncolytic virus with one of the deservedly famous anti-PD1 immunotherapy drugs (Nivolumab) to remove immunosuppression. Oncolytic virus strategies have been looked at for years (this particular virus was first published in 2008!) with somewhat underwhelming results – but I believe the addition of the new PD(L)1 inhibitor class of drugs is making the field poised for a major resurgence. A fun piece of trivia: My primary oncologist at UCSD Dr. Tony Reid is a co-inventor of this virus – he has studied oncolytic viruses for years! Small world, huh?
How do oncolytic viruses work?
You might have seen stories about anti-cancer viral therapy on popular TV shows over the past few years on shows such as 60 Minutes or perhaps HBO’s Vice. Oncolytic viruses are common viruses that have been reengineered to preferentially replicate in tumor tissue. They hone in on tumors, replicate in them, causing them to burst. Cells bursting? Yep, that is a fancy medical term to say the cancer cells get killed 🙂
But oncolytic viruses do much much more. Viruses also do a great job of attracting the attention of the immune system in multiple ways, making oncolytic virus therapy an immunotherapy. As the viruses replicate in tumor tissue – the tissue become highly inflamed and immune system cells become attracted and start to stream in. At the same time, as cancer cells are killed, they release neoantigens from their mutations, essentially a form of on the spot therapeutic vaccination.
In effect – oncolytic viruses convert MSS-CRC “Cold tumors” into immunological “Hot tumors”.
So… in theory – what this therapy is setting up is a situation of:
- Direct, preferential cancer cell killing by the virus
- The virus highly inflames the tumor sites converting my “Cold” MSS-CRC tumors “Hot”
- As shown in an earlier monotherapy Phase 1 trial, immune T-cells stream into the tumor
- Neoantigens arising from mutations in the cancer cells’ genomes are released as a local form of therapeutic vaccination
- Now, in addition… in this new trial, removing immunosuppression with a PD-1 inhibitor after the tumor become immunologically hot and infiltrated with immune T-Cells
How Many Viruses Did You Say Again Willis?
I think I forgot to mention how my viruses get infused into you for these kind of trials. TRILLIONS. Infused directly into your body by iv. To put into context, that is a virus copy for every 10 cells in your entire human body. Massive doses. A lot more than someone just sneezing next to you on the subway giving you a bad cold. Stage IV cancer treatment is not for the faint of heart.
How Does This Tie into My Personal immunotherapy Project?
It may tie in very well 🙂 Once again with thanks to the immunology advice I have received from expert friends… the effects oncolytic viruses have on my tumors may be highly synergistic with my personalized vaccine immunotherapy plans by their: 1.) Breaking down of tumors 2.) Highly inflaming them to activate for immune cell attack 3.) Increasing ability for T-cell infiltration. I will do the current trial monitored by CT-scan. Ideally it will work well on its own – if it doesn’t – it sets me up well for a subsequent blast with my personalized vaccine!
Plans on a Practical Level
Even though I emailed the same day and even though the trial is still listed in the official clinicaltrials.gov database as “Not yet recruiting” – when I arrived for my first available appointment yesterday, there was already a wait list forming – I am #2 on that list. It just goes to illustrate that when you design a scientifically exciting trial in a patient population with high unmet medical need – patient accrual for clinical trials is not a problem!
The trial MD estimated that my #2 slot will open up in 4-8 weeks (they only get to dose one patient at a time) and to be prepared to jump when a phone call from him happens. This is the kind of situation of: they call – you jump – or the slot goes to #3 on the list… I assure you I will have my basketball shoes on 24/7 ready to jump! 🙂
Until that phone call arrives, I’ll continue to tread water with FOLFIRI chemotherapy. In terms of the actual details of how the trial runs, I’ll keep that for a blog post later this Fall – but it will involve a lot of travel to (and some hotel time in) LA for dosing, biopsies, scans, safety observation etc.
Planes on a Taxiway
My overall strategy over the past year and a half has been to lay the groundwork for trials, working around my melanoma issue. As I indicated earlier in the post, I have absolutely zero intention of dying of CRC in my 40’s. Not if I have any say in the matter!
The way I always picture it: My goal is to line up clinical trials like planes on a taxiway… Time for the first flight to take off!
Exciting days lay ahead in the very near future. To Life!