GIST Support WikiThis page is for information related to CNF2024, one of the Clinical Trial Drugs. Feel free to add your own experiences with the drug in the comments section or any other links to useful resources.
[edit] Basic Information
Manufacturer: Conforma Therapeutics, now owned by Biogen Idec
For information from the manufacturer link here
Molecular Targets: heat shock protein 90 (HCP90)
Trial: Phase I trial of this drug is currently underway - follow this link
GIST Support International website page: link here
[edit] Comments from Trial Participants
COMMENTS FROM HAVASU (Kathy and Herb)
5 January 2007 Herb is the first GIST patient to try this particular oral heat shock 90 inhibitor (CNF2024) in clinical trial. CNF2024 is the first synthetic heat shock 90 inhibitor made from a purine scaffold. It is an oral drug.
Some other types of HSP90 inhibitors (17AAG, IPI 504, CNF1010) are in contrast related to a natural antibiotic called geldanamycin. These drugs are also in clinical trial. Infinity released promising proff of concept data about IPI504 for GIST at the EORTC in November. IPI 504 is listed on the GSI web site along with some information about HSP90 itself in cancer biology.
09 January 2007 Day 1 of CNF2024 Pills ((Phase I Trial (oral HSP90))AKA (as Herb refers to) 'Gist Guinea Pigs Local CNF2024' trial Herb arrived at Virginia Piper Cancer Center 7am 01/09/2007 Blood draws every 15 min for the first 2 hours, then every 2 hours (with last draw for the day at 5:15pm) EKG - 7am First pills at 9am 3 blue capsules (100mgs each) (Trial protocol is 300mgs twice a week for 3 weeks and then 1 week washout) Urine collected for 24 hours Herb was monitored from 7am till 5:15pm. In the afternoon, he was allowed to leave a couple times for breaks of a hour or so.
Next day 01/10/2007 9am blood draw again (24 hours after first pills) Kathy's side notes: drug was to be started at 7am but delayed two hours as it took 4 chemo nurses and about 14 sticks before they could find one of Herb's veins that was willing to cooperate. (I had to leave the room, -it was awful). They left the IV in for 24 hours to avoid Herb having to go through this again, -this trip anyway. At this point, we’re thinking Herb should probably discuss having a port installed, -up until this point Herb really didn’t want too.
Herb could actually feel warmth, like hot-flashes from the drug, -most intense about 90 minutes after taking the drug and then slowly tapering off at about 4 hours. His face remained flush for about 24 hours.
Very nice staff at Virginia Piper. (we felt these facilities were much friendlier than City of Hope where we felt like a number and as tho we were cattle being herded through numerous overcrowded, standing-room only shoots.) Virginia Pipers welcomes caregivers to stay and use of any of the unused chemo recliner chairs with small portable TV/headphones on each chair. However, I elected to spend some of the day outdoors, -reading, napping in the van and walking the gorgeous trials that wind throughout the grounds. It was easy for me to take breaks away as the staff is very attentive and personable with the patients. (also knowing they had my cell phone # if needed)
Herb's spirits are good (he's not the type to complain much anyway), -he's a trooper and happy to be part of this trial. So far, so good. Thanks to everyone for your notes, prayers and support. It is so appreciated!
ps First comparison scans will take place 2 months after drug start date. (so it will be two months before we know if the drug is working or not)
16 January 2007 CNF2024 Day 8 3rd dose of CNF2024 Herb's words in response to how would he describe what is happening: 'Well, imagine how your body aches when you have the flu..... thats what it feels like, only much worse the day of taking the meds and the following day.' 'It also feels like my body wants to crawl out of my skin.'
Herb has trouble sleeping for the body aches. He falls to sleep out of pure exhaustion, -only to be up an hour or so later with the aches. He has slept twice, -a total of one hour each time in the last 24 hours.
He is not complaining (altho he doesn't look to well at moments), -says if it works its worth it. They have decided to scan him after one month of the drug (versus waiting 2 months as in trial protocol) to see if the drug is having any effect on his tumor. Herb says it feels as if there is definitely a war between the drug and the tumor going on at the tumor site. We hope and pray the drug is winning the battle!
30 January 2007 Friday morning, 01/26/07 Herb swallowed his pills for the end of the first cycle of CNF2024.
A CT/PET fusion was given Friday night. The CT/PET shows no change from 3 weeks earlier. The CT/PET is still just as hot (7.2), but not any hotter.
Apparently a CT/PET fusion cannot show if tumor has decreased or increased...... A CT/PET fusion is not that precise. To know that, would require a CT. A CT was taken 3 weeks ago and another CT will be given at the end of Herb’s second cycle...... So at this point, I guess we have to wait another month to know if CNF2024 is truly working or not.
We had hoped the CT/PET fusion would tell us. Normally, I guess it would, as it would be either hotter or colder.......so until he has a CT next month, we really just don’t know if the CNF2024 is having any effect or not. For now, we’re accepting it as stability and onward to cycle 2.
ps You will not find a nicer staff anywhere as those at Virginia Piper!
3 Mar 2007
After two months of CNF2024 the results are mixed. One large tumor decreased by 2 cm but some of the small tumors became larger. The PET is hotter than last month in some areas, but colder in others.
A very confusing and frustrating mixed bag, however we grateful the larger one has decreased! So I guess we can assume the drug will be effective on certain gists, however will it powerful enough for those like Herb, which have huge tumor loads and have carried those huge tumor loads for over six years and two prior drugs?
They will try to see first by having Herb take the drug through washout next cycle. Maybe another possibility down the road would be a higher dosage.
A good note is that they have found some drugs that have been a tremendous
help with some of the side effects Herb was experiencing.
Wish we could report another miracle breakthrough. Not as good as we hoped, but not as bad as it good be I guess. We are not giving up that this drug may still hold promise!
1 May 2007
When it rains it pours-we found out yesterday that CNF2024 is not working for Herb and that his small tumors have grown into his large tumor to where they can't even differentiate them apart on a scan. His PET is very hot.
3 Jun 2007
Subject: Herb Flom Update - Intestinal blockage
We just got back from Summerlin Hospital in Las Vegas where Herb had emergency surgery starting at 10pm Friday, 05/22/07 for an intestinal blockage due to the gist in his abdomen squeezed a middle section of his intestines off.
It all started when we went to the dr on Wed 05/20. The Dr scheduled CT's, ect. for Thursday morning which showed the blockage and they immediately sent us over to ER. Herb stayed in ER for over 30 hours till surgery at 10pm Friday night. He stayed in ER due to no hospital beds/rooms available while he waited. (Surgery was scheduled for 3pm, which got moved to 5pm, then 8pm till it finally happened at 10pm.)
His blood pressure bottomed out during surgery and they brought him back by immediately giving him a blood transfusion and fixing the massive bleed caused by the tumor rupturing as the dr attempted to fix the blockage.
The next 6 hours after surgery were the most heartbreaking of my life as I watched my husband in horrible pain as they felt they could not give him any more pain meds due to they felt the pain meds would bottom out his blood pressure (again). Herbs blood pressure was off the charts low and heart rate was way to high. Herb has been on pain meds for years so what might be adequate for most people, were not phasing his pain. I will spare you all the details but I could not take him pleading and begging any longer and finally told them that I was making the executive decision and what will be will be....give him relief..... Soooo, they did..... and a miracle happened...... exactly opposite to what they predicted..... slowly his blood pressure went up and his high heart rate went down.
A prayer answered.....
It was by far the toughest decision I ever had to make in my life......I finally came to the agonizing conclusion to insist on pain relief as I felt if in his shoes it was what I would want for me. Enough was enough. Thankfully, it was the right call and did not go the direction the Dr thought. When Herb got better and I told him what transpired, -he could not thank me enough for not allowing that kind of pain to continue. Herb says he was fully aware and remembers all to well the pain he was in and begging for relief, -he says w/o a shadow of a doubt increasing the pain meds was the right decision....even if the outcome would have been different...... -relief is what he wanted and never to be in that kind of unbearable pain again.
I thought I was so prepared.....-I had been taught there is no excuse for allowing a stage 4 cancer patient to be in excruciating pain..... but I had never anticipated this....(that Herb's blood pressure could bottom out (again) if too much meds given).
After arriving home, Herb found getting in and out of bed was too difficult so I had an elec hospital bed delivered and now Herb can get up and down ok on his own with the remote to help raise and lower him.
Just minutes prior to surgery, the surgeon told Herb that it would be a very remote chance he would be able to just reconnect the intestines and fix the blockage as he(Herb)wished and if he couldn't, should he place a feeding tube in and tubes out or just sew him up. Herb replied he wanted it fixed right as he wanted to continue in trials......the surgeon said,I know, but what if I can't -Herb said that is what I want, -just reconnect me. The surgeon and Herb went about three rounds with the surgeon asking the same question and Herb giving the same answer. Then in frustration they both looked at me, -(note - Herb has been adamant throughout this 6 year journey with an huge inoperable tumor that he didn't want tubes/bags ect....Herb has always said that if there were no drugs to hold the cancer and he were in his final days that he didn't want it to be this way. Herb also felt that feeding tubes ect. would disqualify him for the trials he was seeking. So Herb was determined that the Dr fix it so he'd have at least a shot at what might be the next miracle drug.)
After surgery the surgeon came out to speak with me. He told me it was a very difficult surgery due to the tumor rupturing and Herb's blood pressure bottomed out, but they were able to bring him back and he was able to do as Herb wished. He said the cancer was everywhere he could see, -side to side, up and down. The surgeon had removed gist tumors before, but had never seen anything like this, and none that had been through gleevec and sutent and the surgeon said they were entirely a different consistency and thanked us for warning him and being immediately ready with the transfusions.
Next weekend our youngest graduates from High School, -Herb told her I'll be there! She said, that's ok Dad, I understand, its ok, don't worry about it, we'll take pics. Herb said I WILL BE THERE, and NOTHING can keep me away. (we will send a pic of the event to the gsi photo gallery, because I too know he will be there.)
Sorry this is so long, thanks for listening.
Herb dx 01/2001 with football size inoperable tumor in abdominal area wrapped around all vital organs
02-2001 = 07/2004 = 800 mgs gleevec trial
08/2001 = massive heart attack = (left with 38% permanent heart damage)
09/2004 = 10/2006 = Sutent trial
01/2007 = 04/2007 = CNF2024 trial
July 2007
Herb lost his courageous battle against GIST. Our prayers go out to Kathy and their children. We thank Herb and Kathy for sharing their experiences for the benefit of all other GIST patients.