GIST Support WikiThis page is for information on XL-820, one of the trial drugs. If you have any knowledge of this drug and would like to share it with the group, please enter your post below. In addition, you can add links to other pages/sites with information on this drug. If you have questions about entering your information, please contact us via the Wiki Team page.
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[edit] Basic Information
Manufacturer: Exelixis
Molecular targets: KIT, VEGFR2/KDR, and PDGFR beta.
Trial: phase I trial [1]
GIST Support International website page on XL820: [2]
Comments
5 Dec 2007
From: Brad Subject: Re: xl 820 phase 2 trial for gist
It was just announced that xl820 is being advanced to phase 2 for gist. What is known about this drug? Is anyone currently on it? From the announcement it looks as though you may not have to fail sutent.
Wed, 5 Dec 2007
Subject: Re: xl 820 phase 2 trial for gist--BRAD
I think XL820 might become to GIST, what dasatinib was to CML.
I have been tracking this drug since Nov 2006, when I met Exelixis representatives at the EORTC in Prague--in the conference hall and in the Prague airport.
GSI has been raising awareness about the phase I trial (in San Antonio and New Jersey) for the last year. The drug works similarly as Sutent, BUT it can block some resistance causing mutations that Sutent can not block--in the "Activation loop" (exon 17). THe key is whether the drug has the right pharmacological properties in the bodies of GIST patients (metabolism, and ability to enter the GIST cells in effective concentrations).
The GSI webpage about the current phase I XL820 trial: http://www.gistsupport.org/treatments/emerging-treatments/inhibitors-of-kit- pdgfr-or-vegf/xl820.php
You may need to copy and paste the URL into your browser. The GSI webpage for XL820 will need updating once phase II trials start. Also there is a great poster from EORTC 2007, that we need to include.
Brad--Your oncologist elsewhere mentioned getting this trial too--I don't want to mention names on the listserv as this doctor may not have wanted that information public. Jim Hughes from LRG reported yesterday a phase II site in Illinois.
Like Sutent, XL820 has a higher affinity than Gleevec for "wild type KIT" and almost assuredly for exon 9 mutant KIT.
A combinaton of Sutent and XL820 blocks a large majority of ALL known secondary mutations that case Gleevec resistance.
Preaching from my soap box:
Sorafenib is sounding good. IPI504 sounds good and works by an entirely different mechanism. IPI504 has the potential to wipe out KIT protein with multiple mutations in it, which is harder to block treat by the kinase inhibitors (Gleevec, SUtent, XL820, sorafenib, OSI930). Histone deacetyalse inhibitors, flavorpiridol (cell cycle inhibitor at MSKCC). MP470 by Supergen is in Scottsdale, and it too blocks some of these "A loop" mutations that are resistant to both Gleevec and Sutent.
For the scared resistant patient--fight your disease incrementally--do the best you can to buy time right now, there may not be a single "one step" that solves your problems--so don't pass up opportunities to push your disease back because you know they aren't the ultimate solutoin. Go ahead and take those many smaller steps.
To the lone resistance fighters, stay strong psychologically, make smart decisions to fight your disease how you can right now, I think "help is on the way" Big pharma and biotech are delivering drugs into the pipeline now that can help you. There seem to be many ideas out there, many trials.
I have a link to the XL820 poster from EORTC 2007. I will post it later, with a discussion about what the poster is telling us regarding this new drug.
Exelixis also has other interesting drugs that block another important target in GIST, PI3K. XL765 blocks PI3K and mTOR. IT is available in San Antonio.
Marina
[edit] Comments from Trial Participants
[edit] Floyd
14 Feb 2008
My husband, Floyd, will be starting the XL820 trial on the 26th. He had been on Gleevec and then on Sutent. His last scans showed growth again so Dr. Wagner at Dana Farber has suggested that he try the XL820. Has anyone else been on it - and if so how is it?
Also, we live in Richmond,VA and when he starts the XL820 he will have to go to Dana Farber every 2 weeks for 8 weeks and then every 4 weeks. Does anyone have any suggestions regarding cheap as possible airfair or motels?
14 Feb 2008
Subject: XL820 trial
Part of the XL820 trial is "optional" biopsies done at the beginning of the trial and then after the first cycle of the drug. Floyd does not want to have them done. He is afraid of the risk of the biopsy causing spread of the disease. Is there any benefit to him for the biopsy or is it only to gather info for the study, does anyone know? I thought he should have the biopsies but I want him to do what he is comfortable with. Any advice?
Cindy
14 Feb 2008
No, we don't know his original mutation. He had his first and only biopsy done at St.Joseph's hospital in Tampa FL. The path report didn't mention anything about it. The follow up visits every 2 weeks are more than just blood work. They will include hair samples, cheek swabs, and urine samples before and again four hours after taking the medication that day. So I don't know if an alternative site for the blood work would work.
2 Mar 2008
Subject: Re: boston and xl 820
Brad, I hope everything goes well for you in Boston. Floyd and I just got back from there Wednesday night, he also just started the XL820. He is taking 800 mg once a day. Let me know if that's what they give you or if they give you the 300 mg twice a day and what if any side effects you have from it, please.
Cindy
29 Mar 2008
Subject: Re: brad's xl820 trial
We just got back from DFCI last night. Floyd had his one month scans done on Thurs and saw Dr. Wagner yesterday. His first words to him were "Congratulations on your scans!" They showed that his tumor has decreased in size a little and that the pet scan showed 25% less activity.
Brad, I'm so glad that you also had good news. Floyd also has more fatigue than with the Gleevec or Sutent, but much less diarrhea than before and really no other side effects. We are so thankful for the progress.
Cindy
[edit] Brad C
28 Feb 2008
Subject: Re: boston and xl 820
Well I am back in Boston to go through the final testing and to begin the xl 820 trial barring any unforseen problems. I have been on a 2 week gleevec washout as required for the trial and must admit I've enjoyed the vacation. Obviously I am hoping for some success with this trial but am trying not to set my expectations too high as I am not excited about further disappointment. It is great to see others doing well and that does give me hope. Hopefully the side effects will also be manageable. If I have success on this drug I hope that it will provide encouragement to others. Regards, Brad
22 Mar 2008
Subject: Re: update
Hi all. I have been on xl 820 for 3 weeks now and am now dealing with extreme fatigue to the point that I have slept most of the past 2 days. I also have a painless itchless rash on my lower legs which is now feeding. Lastly I have what I would call a sinus headache which moves around toward the gravity down side of my head and have been experiencing a slight fever, which I suppose could be from tumors or from a sinus infection. My knees also ache and I am getting cramps in my legs and hands. This all started after I drove to the nc mountains for a fly fishing trip. Stopped and saw Bob for breakfast in Ocala on the way home but I also flew out of atlanta to boston and back as a part of the excursion. At boston dfci my hemoglobin was as high as it has been since my first surgery and I was told my liver functions all looked perfect.
Any ideas from those that have had to deal with extreme fatigue? Btw on palpitation I was told my liver felt normal. I guess I'm a little baffled. Brad
29 Mar 2008
Subject: Re: brad's xl820 trial
Had my one month cat and pet scan for the xl820 trial at dfci yesterday and am happy to report that preliminary results are that it is WORKING! I am stable to shrinking and all indicators are that it is being effective. I received the news last night and will sail through the weekend and get more details on monday. As one of the first trial patients I have experenced fatigue but little else. I encourage others to keep trying and do not give up the fight. There are too many resarch possibilities our there now to relinguish the battle with gist. Brad
1 Apr 2008
I want to thank everyone here for their words of support and encouragement. My fatigue seems to be improving somewhat. They will be checking my thyroid function. After one month on the drug I had about 10 percent shrinkage a decrease in density of the lesions and a decrease in pet uptake. The growing lesion looked much less dense and colder. Based on Choi criteria I was told I've had a partial response. We shall see how things look next month. Brad
5 Apr 2008
Subject: Re: rash on kinase inhibitors
As some of you know, I am on the xl820 trial at dana farber. This week I had a head cold and within a few hour I develped an itchy almost burning skin reaction which looked like bright red raised splotches on my skin. First behind the knee then spreading to my legs and arms. Also a few on my torso. I went to the local oncs office which gave me iv benedril and a oral pack of predisone. This helped but it has come back several times while almost clearing completely after taking a benedril. I am off xl820 til monday when I think they will try to intoduce a lower dose. Until this time I had no rash or skin problems and had been taking the drug for over 4 weeks. Any similar situations that anyone has had to deal with? I really don't want to stop the drug because of this and would appreciate any advise. Brad
5 Apr 2008
Subject: Re: rash on kinase inhibitors
Brad,
I developed a severe rash after about 4 weeks on Gleevec. They took me off the drug and sent me to a dermatologist who did a biopsy of one of the raised, red rashes. I have had psoriasis since I was about 15 years old and this was my psoriasis reacting to the Gleevec. They didn't reduce my dosage of Gleevec, but put me on a steroid cream and then gave me a drug - methotrexate - which is known to help psoriasis patients.
That was last July. Recently we tried to reduce the methotrexate dosage and the rash came back rather quickly. The moral - I need to stay on the methotrexate in order to tolerate what Gleevec is trying to do to my psoriasis.
I know it's not like yours, but if they find the right combination to keep the skin rash under control, you should be able to take the XL820.
Good luck, Margo from MASS