The Colon Club

I'm interested in the trial for Napabucasin combination with or without Avastin. I am intrigued that it could resensitize tumors to Folfiri and Avastin and seems to have few extra symptoms. Has anyone here joined this trial yet?
NCT02753127

https://clinicaltrials.gov/ct2/show/NCT02753127

While I don't have info on this. I am bumping this thread back to the top. Maybe Maia has some helpful info.

Hope someone can help you,

Lee

My husband and I are going to Mayo Clinic on March 20 to see if he is eligible for this trial. Will let you know what we find out...

I called in to one of the trial sites in my area ad they took my info. The trial nurse said I'm not a candidate because I am currently on Folfiri. I'm shocked and very disappointed. The press release from Boston Biomedical reads, "this phase Ib study showed that napabucasin (BBI608) at 240 mg twice daily can be combined with FOLFIRI with and without bevacizumab, and demonstrated early anti-tumor activity in heavily pretreated colorectal cancer patients, even in those with prior progression on FOLFIRI-based therapy".

The drug is resensitizing patients to Folfiri yet they say I'm not a candidate because I'm already on Folfiri. The inclusion conditions on the info sheet don't say that in my eyes so I'm going to call a different trial location and see if their interpretation of the inclusion conditions is different.

KElizabeth, can't write too much now but BBI608 or BBI-608 is a proposed cancer stem cell inhibitor, oral, not immunotherapy, that is in phase III trials, with a tolerable side effects profile and good results. Something to "tread waters" while waiting for a highly promising immuno trial (that's the way people lining clinical trials see it, strategically). There are *many* trials with that agent, in different combinations. Use the ct finder.in my signature (curated by DK37/ Tom Marsilje), searching for the drug name.
Will be back tomorrow to comment what you get!
Not in this forum but i know several who were or are in trials with this.

Search in this forum, there are posts from me in 2012 or 2013 about this drug.

Update.
I've now inquired at all three local trial locations for this trial with no success at getting to an application but for different reasons at each site.
1st site said that I could not be part of the trial if Folfiri has stopped working for me. We haven't decided yet if it has.
2nd site said that I couldn't be part of the trial unless I have failed on Folfiri (The opposite of what the 1st location said).
3rd site said they are no longer in the trial.

I'm really getting frustrated with the process.

Sorry to hear.
What locations might work for you? Why aren't you interested in a trial with some immunotherapy? (Like one with this same BBI608 + checkpoint inhibitor, for example)?

Maia wrote:Sorry to hear.
What locations might work for you? Why aren't you interested in a trial with some immunotherapy? (Like one with this same BBI608 + checkpoint inhibitor, for example)?

Really the first reason I location. I would love tof keep my job, home and lifestyle if possible. I live in Omaha and I am a reasonable distance to Des Moines and Kansas Ciy.
The second reason is I'm freaked out that the immune response may be unpredictable for me. I have a goofy system and meniere's disease too boot. I am almost certain I am MSS, so I am hesitant to jump into a trial that could unleash my immune system on me without knowing there is benefit to MSS patients.
I'm working through the MSS issue but it's like pulling teeth and too long ago story to mention right now.

3rd reason is that folfiri has treated me pretty good, and this looks very promising for resensitizing to Folfiri. Sometimes it's better to stick with the devil you know.

Totally sensible reasoning. I do know that Folfiri can be very manageable for most people, even with huge dose reductions, and not loss of effectiveness.
Are you KRAS wild or mutated?

Maia wrote:Totally sensible reasoning. I do know that Folfiri can be very manageable for most people, even with huge dose reductions, and not loss of effectiveness.
Are you KRAS wild or mutated?

I'm KRAS mutated and it's my driver. I went through phase one of the Match trial to find out I am not a match, but gained some other data. My tumors is showing APC mutation which is responsible for FAP although I tested negative for FAP when I did genetic testing with Dr Lynch and it shows a mutation to TP53 which is more common in leukemia or sarcoma.
Not sure how this will help me, but I find it interesting.

I'm contemplating trying to get into the RENCA macrobead (mouse renal adenocarcinoma beads) trial that has a location in Kansas City too. I am impressed with the results of phase 1 and I like that it is just a few treatments. I'll probably call for info today.

The RENCA trial might be a good option.

I will mention this study because, even if it is in Arkansas, a bit more far away than your location zone, it uses two oral agents (two pills), so maybe not so many trips are required, it's for KRAS mutant CRC patients. One of the agents was experimental until two weeks ago, but got just FDA approved. Targeted agents, not immunotherapy.

*For KRAS mutant.
*Non measurable disease accepted in phase I.
*Open-label, non-randomized.
*No immunotherapy but a combination of targeted agents (small molecules)
*Trametinib + Ribociclib (Mekinist, a MEK inhibitor, Oral + an inhibitor of cyclin D1/CDK4 and CDK6, Oral)
*In Phase I, admits patients with all metastatic KRAS-mutant *solid tumours* "who have failed at least one prior line of systemic antineoplastic therapy in the advanced setting without a standard of care treatment option available". Non measurable disease accepted;
*For Phase II, only KRAS mut CRC are accepted; phase II requires measurable disease.

https://clinicaltrials.gov/ct2/show/NCT02703571

Ribociclib ( inhibitor of cyclin D1/CDK4 and CDK6, Oral; previously it was called LEE 011, now the commercial name is KIsqali, manufactured by Novartis) has been approved past week for breast cancer (https://www.fda.gov/Drugs/InformationOn ... 546438.htm ), so using is now would be off-label.

Thank you. I'll inquire about logistics on this. Looks promising.

If you can't get into the RENCA trial, you might consider a very similar one using Pfizers well established CDK4 Cyclin D inhibitor Palbociclib in combination with their most recent MEK inhibitor PD-0325901. This drug combination would be very similar to that in the RENCA trial.

See: https://clinicaltrials.gov/show/NCT02022982

Both these drugs came out of the Ann Arbor research Labs of Parke Davis (PD) and sat on the shelves for a long time when Pfizer took over Warner Lambert Parke-Davis. The MEK Inhibitor is a newer generation of those worked on for many many years at PD (CI-1040), finally seeing the light of day. I worked on some aspects of the synthesis of Palbociclib early on. My colleagues and friends in the group worked on the MEK inhibitors. Looking at the structure of PD-0325901 I am sure it is just the latest generation of MEK inhibitors based on the early work.

A Comparison of the CDK inhibitors are discusses here:

http://www.hematologyandoncology.net/in ... st-cancer/

Note that these drugs are primarily used in treatments of breast cancer, but could prove to be useful especially in settings where the tumor type might be susceptible to these combinations. Many Breast Cancer cell lines were shown to be particularly susceptible to these classes of drugs hence initial development along these lines. I suspect that as more is learned we will see this turn up in some people as treatment for other solid tumor types.

Mek Inhibitors have found use in Melanoma primarily I believe, but as you see in combination with other agents may cross over into other tumor types.

Good luck in your treatment search.

GrouseMan

My husband and I met with an oncologist at Mayo Clinic on March 20 regarding BBI608 and FOLFIRI +/- Avastin. Oncologist told us there are currently 91 open slots in the trial nationwide. He also said that in initial Phase I trials a few years back, the side effects of BBI608 were so harsh he had little hope for the drug. He now feels very positive about the results they are seeing, and said they seem to have found the "sweet spot" for dosage in terms of limiting side effects.

Most recent scan last week showed control/minor shrinkage on Xeloda/Avastin, so we are sticking with that for now and keeping trial in our back pocket. Just thought I'd share for those interested.

(Trial info again, https://clinicaltrials.gov/ct2/show/NCT02753127)