Paul's experience on the Cediranib (AZD2171) trial

[Paul]

NEW DRUG ALERT!!!

This drug works the same as PXD101 ie. it prevents or slows the production of new blood vessels that 'feed' the tumor, thereby slowing/stoppiing/reversing tumor growth.

It has shown to have a positive effect in a number of trials before and as my Doc (Prof. Ian Judson, London) tells me on other asps patients as well!

What is also exciting about this drug is that it seems to work in the brain, whereas the PXD molecules had no effect (they were too large) the AZD are apparently small enough to pass the blood - brain barrier and prevent new growth! They have even in a number of studies on other cancers reduced tuor size by 25 - 50%. What this means for asps brain mets I don't know, all cancers are different beasts but we shall see.

It is given orally and is in a Phase II clinical trial at the Royal Marsden Hospital, London. If you google 'AZD2171' or 'AZD2171 brain' as I rather cunningly did (!) you get a load of info.

If anyone wants any other info. please just ask questions. If it is urgent please e-mail me as well as I am a bit slack at checking the site.

All the best, Paul x

[Paul]

PS my e-mail address is; mavsyboy@gmail.com

[Olga]

Paul, thank you for alerting us reg. possible activity of this new drug AZD2171 in an ASPS brain mets setting. I have checked the clinicaltrials.gov and could only find a few trials in US open for the young people (less then 21) with the primary CNS tumors
http://clinicaltrials.gov/ct/show/NCT00326664?order=13
and for solid tumors incl. sarcomas but for the young people less then 18 years
http://clinicaltrials.gov/ct/show/NCT00354848?order=7
the rest of the trials are for other indications or run in Europe. So it seems that Astra Zeneca is going to finish in Europe first, we hope that in case of the success/promising result Pf.Judson will present it on the CTOS or other relevant meetings or more trials will be open in the future. There is alos a trial open at the MD Anderson in Texas testing the combination Avastin+AZD2171 for Metastatic or Unresectable Solid Tumor or Lymphoma. AZD2171 will have the name Cediranib in North Am., it may be different in Europe.
I wanted to ask if there was any response in the lung mets to this new drug AZD2171, are you still on it?

[Paul]

Dear Olga,

I have not started on the trial yet.

Yes it works throughout the bloodstream so it if proves to be successful in the brain it would work just as well throughout the body.

I will let people know how I get on, posting every now and again on this thread, and will ask Prof. Judson about the drug in other countries.

All the best, Paul x

[Olga]

This is the news from Paul Mavers who is on the clinical trial for AZD2171 in UK from about September 2007, I think the trial is under the supervision of Pf.Judson who is very well known and might be contacted by your oncologist (I hope that Paul will be able to post the comment on it by himself but in the mean time I am posting this encouraging mid-term results for other patients who might take it into the consideration when looking for the appropriate clinical trial that is promising for the brain mets):

I must let you know that the AZD2171 has had extremely positive results, both in my body and more importantly in my brain. After the first two months my brain mets had reduced by 10%, after the next four months (I just got my results recently) some brain mets had remained stable and one had reduced again by around 10%. At the same time all other mets have remained stable and/or reduced, some by more than 10%! Everyone starts on 45mg, all others have had to drop down to 30mg due to side effects but I have been lucky and been able to stay on 45mg. I have never suffered too bad with side effects on anything, thankfully.

AZD2171 (Cediranib, Recentin) is only avail. on the clinical trial, there are some trials in North Am., the most appropriate one for the soft tissue sarcomas is in the Young Patients setting - up to 18 years old but probably the exception can be done using the evidence of its activity in Paul's case if Pf.Judson will be willing to provide a back up. It is open at the Warren Grant Magnuson Clinical Center Bethesda, Maryland, United States and Children's Hospital of Philadelphia, more info at www.clinicaltrial.gov

[Paul]

Hello everyone,

I may not be well known by some on this board, and maybe forgotten by others, as it has been a long time since I have posted here. I would like to fill everyone in on the success I have been fortuunate enough to have with this new clinical trial.

I am based in London at the Royal Marsden Hospital (a cancer specialising hospital) under Dr. Ian Judson. I have been taking part in the trial for over six months now, and have had positive results throughout.

RESULTS:
I have had three scans since I first began on the trial, at 8 weeks, 16 weeks and 32 weeks (I think these are the correct times, I may be slightly wrong)!

8 weeks: No new tumor growth, a good number of tumors in my lungs and one in the muscle tissue of my back had reduced in size by 10% or more. I have 3 tumors in my brain the largest at that time was 15mm. All brain tumors either showed stability or around a 10% or more reduction in growth.

16 weeks: No new tumor growth. Again there was a slight reduction in some tumors, including those in my brain although the effect was not as pronounced as before.

32 weeks: Again there was no new tumor growth. Again there was a slight reduction in some tumors, including those in my brain and once again the effect was not quite as pronounced as at 16 weeks.

I am still on the trial and below I have listed the side effects I have been dealing with. Here it is worth noting that I have managed to stay on the full 45mg dose of this drug, I am fortunate as everyone else on the trial has had to have their dose reduced to 30mg as some or all of the side effects have been too much. I will only list what I have had to deal with, a full list of side effects can easily be found with a rudimentary google search.

SIDE EFFECTS:
Side effects for me have included (from most prominent to least), diarrhoea (this is common, happens to me a lot throughout the day and night and is accompanied by sometimes quite painful stomach cramps), sore throat (again common, this is often accompanied by a hoarse voice, which can be sexy or so I'm told, and has meant for other patients they have unfortunately had problems with eating their food), problems eating spicy foods (although by no means a serious problem your taste buds on your tongue enlarge, spicy foods and anything hot in temperature are problems), tiredness (this effects more sometimes than others and means I sleep a lot occasionally, nothing new there then!).
In terms of side effects this is it for me, I am lucky. Others have had more problems.

I think this is all the details I have for the moment regarding this trial. I will post new information up here when I get it and keep you all informed the progress. I wish everyone well and if anyone would like ANY information on this or anything else please feel free to e-mail me at: mavs_1357@hotmail.com

All the best everyone, lots of love, Paul X

[Ivan]

Congrats, Paul. Very hopeful result so far.

[Beth]

My son's doctor contacted the NCI CTEP program (http://ctep.cancer.gov/requisition/compassion.html) to request release of this drug for my son, who has been plagued by brain mets, based upon compassionate use. The investigators responded that given the severe toxicities of the drug and the lack of data for its use in soft tissue sarcomas, they will not release Cediranib to us. This was so disappointing. Here we have our dear friend in the UK sharing his information, but it is just anecdotal by the program definition! Of course we won't ever have a significant amount of data to persuade any NCI investigator when their guidelines are defined by a norm that we can never attain! catch 22.

*Paul -- I'm thrilled and so very happy for you! -- hope you don't mind my use of your good news to shout out my frustration!*

[Olga]

Beth, I know that Bonni and other people contacted Pf.Judson regarding the long distance enrollment into their trial but he said that it is closed for accrual, I do not know what is the time line there, when the result is announced - then it can be used to get the drug on the compassionate basis. You might contact Pf.Judson to ask. If this is the study that Paul was on
http://www.clinicaltrial.gov/ct2/show/NCT00264004
then its estimated Study Completion Date: May 2008
May be your son can be accepted into the pediatric trial at NCI - 'F' managed to persuade the accept 'K' into the adult trial.
http://www.clinicaltrial.gov/ct2/show/NCT00354848

[Fictional]

Wow - pictures speak louder than words. I saw that Olga just posted that Judson's group is going to present about Cedirinib at the latest ASCO, so I google searched and found out that the hospital's research group has published this update on sarcoma that includes pictures of the response of ASPS to Cediranib - both lungs and an axillary mass. It is pretty dramatic folks take a look (figure 1):

http://www.icr.ac.uk/about_us/annual_re ... t/9718.pdf

I have also seen that Cedirinib has at least made it to Phase III for colon CA, so at least for the time being there is little chance of it being shelved. I wonder if once the data are formally presented if we could have more success obtaining for compassionate use.

Because this patient was on Cedirinib for so long, is this another ASPS patient and not Paul?

Very cool.

[Fictional]

p.s. It looks as if Astra Zeneca has expanded clinical trials involving AZD2171 -

More sites are open and ASPS patients could be eligible for a variety of them (Canada, Texas, Bethesda...)

http://clinicaltrials.gov/ct2/results?term=AZD2171

[Olga]

Some of these trials have brain mets limitation, the other ones that are in Canada listed as open but do not enroll as according to our oncologist who is supposed to supervise this trial in Vancouver, Astra Zeneca did not give them a drug but since it is still listed as open I hope that they are in the process of something:
Phase 1 Study of the Effect of Ketoconazole on the PK of Multiple Doses of Cediranib in Patients With Solid Tumours
http://clinicaltrials.gov/ct2/show/NCT00750425
Our trial is going to investigate Ketoconazole added to cediranib and I actually have no idea why, it is a synthetic antifungal drug.
The other ASPS patient on a trial could be Clare (I can ask her) but it could also be Paul. Wait for the article on the CTOS and we'll see how many of them were there with the positive response. The other question is a durability of the response. We had people responding to the Avastin and ABT-510 (thrombospondin-1 analog) with the durability of the response of only a few month a speedy regrowth afterward.

[Fictional]

At least this response from the UK (in the figure) indicates after 15 months on the drug. That is pretty good.

You are right that the Avastin benefit was short-lived.

Also, it may be worthwhile for people who have had tumors resected (so tissue blocks in their hospital pathology depts) to ask their doctors to kinase type them. Clarient is a major reference lab in California- and we heard they are now able to test for met using immunostaining...all you would need to do is have the hospital forward the blocks...they do this all the time. Arqule found that some of their non-responders to ARQ197 did not express met in their tumors. Clarient also does staining for VEGF and PDGF.

Our typing was paid for by a charitable group, but the accidentally the last stains (for her second surgery) were billed to our insurance (Premera) and to our surprise, the insurance paid for it all (we are already over our out-of-pocket max because of the surgery).

This might also help with medical decision-making. When we were trying to be allowed access to the drug although we didn't met criteria for their study, we did present evidence that 'K''s primary had high expression of c-met. Please feel free to email off list for any additional instructions on how to do this.

[Paul]

BRIEF UPDATE:

I have remained on the AZD2171 trial since I last posted, I will summarise my results and side-effects.

Results

The last two-monthly scan (I got the results about a month ago) showed a 'stable' disease. I pushed the oncologist on this as sometimes a stable disease can actually show small signs of growth and he came back saying there had been a tiny amount of growth in my brain mets (or one of them, I can't remember!), something like a mm or less. He didn't look at the lung scans as they weren't readily available however I have another scan soonish so will find out more then. Considering I have been on the drug for a year now and this is the only growth I have had from any of my scan results this is pretty bloody good! All other results have either been stable or shown a decrease in met size. Anyway I got given three more months of AZD2171 so I went away happy.

Side-effects
My side-effects are exactly the same as my previous post. I get tired due to lack of thyroid activity (I have thyroxiine for this but don't take it as much as I should as I prefer to put as few drugs in me as poss), I have stomach problems still and the occasional sore throat (maybe the sore throat isn't as bad as it used to be, maybe due to my body becoming accustomed to the drug?) so everything is pretty much ticking over on that front.

I must say everyone should push for this drug in the States, it is deeply upsetting for me to hear that other people are not getting the chance to be on the drug I am on, I know it works and how much it would benefit others. Please, if there is anything anyone can think I can do to push the case for AZD2171 let me know. I have been a year on this drug now and have had a net decrease in the size and quantity of my mets, in brain, bone and lungs.

All the best everyone, I am thinking of you all and send you all my love, hope, courage and strength,

Paul

XXX

[Olga]

Paul - thank you so much for posting an update, I sent you a question last night but my e-mail is not working due to the web-hosting problems so I went to see what is new and was very pleased to see your response about your continued well being on this drug. I want to point out that there are a few locations in North Am. where this drug is accessible on a trial for solid tumors indication in a phase 1 studies - Vancouver and Toronto in Canada with added ketoconazole for a few days from day 8 and for cediranib alone for kids up to 18 years in Warren Grant Magnuson Clinical Center, Bethesda and Children's Hospital of Philadelphia, also combination trial at MDACC for patients with no brain mets. The CTOS meeting is approaching and may be as a result there will be phase 2 for ASPS open in US (I dream). Pf. Judson does his part well and I am anxiously waiting to see his presentation on the CTOS 2008 meeting to check if the result was reproducible, that the side effects were manageable and there was no accrued resistance in other ASPS patients. May be we should all write to Astra Zeneca or Pf.Judson is already doing the lobbying on that front. May be they expect to get an accelerated approval for ASPS,but may be they do not care about ASPS since there is no market volume in it.
Also thank you for letting us know that there is a lack of thyroid activity with cediranib.