My trial has been cancelled.

[susan400]

I just got called by the study nurse.  The trial I was in was cancelled because 3 patients had elevated bilirubins.  For now, the plan is for me to stay on SOC until my follow-up appt. next Wed.  Dr. mentioned that he'd like for me to consider rolling over onto Boceprevir if I can find a way to get it paid for, since I've already been on the SOC for 9 wks.  I will be unblinded on my viral loads and will find out if I was getting the placebo or the study drug; but that information wasn't available when she just called.  My brain is feeling confused and honestly, I don't even know where to start.  I have insurance, but these drugs aren't on their formulary and it's a sh*tty insurance because it's Medicare Advantage.  So, I'm not sure if the drug company will enable me to have any patient assistance.  My husband started a new job and was adding me to his insurance, but he doesn't have any paperwork or card on that yet and I don't have any idea whether it's in effect, or if it will even cover such expensive drugs right out of the shoot.  Part of me feels like giving up and saying that's it, I've had it, no more I quit.  Because I'm just so tired of trying to get SVR.  But, the other fighter part of me, says, what do I have to lose by trying?  I don't have any desire to wait another 5 yrs for all oral treatments, so that's not even on my radar screen.  I've been doing treatments on and off since 1997 and I am wanting to get on with my life.  I just wanted to let my friends here know what I found out.  Susan400

[susan400]

Thanks, everybody.  I will be a good day.  No shot last night (which would have been shot night), no Riba last night, no Riba this morning.  Now, I can try to get back to 'normal' whatever that means...   Susan400

[eureka254]

It was such a disappointment initially, but I'm glad to hear your visit with the doc was a good one and he's already eyeing better horizons.  No doubt you needn't have suffered more with treatment, and I'm glad that you can focus on your family and I hope the time away with family heals both you and your mom quickly.  The new line of non-INF hcv meds look like they might be worthy of an opponent to hcv as tough as you, and it looks like between you and the doc connecting the dots, the picture of cure is sure to come into focus for you soon.  Big hugs, and stay strong and steady.  ~eureka

[crossroadsec]

I may have already posted on here while I was on hold on the phone. lol... I went back to read it again. Your story is extremely poignant. You fight with such intensity, but know how to move past the disappointments. I stand in awe. I'm trying to face my struggles w/ the same spirit. Crying and praying sure helps... Karen :) xoxo

[willing]

that information certainly  sheds light on the road ahead.  Regardless of resistance issues, a 1 log drop at w8 means it's unlikely triple tx is worthwhile. Same applied to  the tela attempt four years ago.  On the positive side, it's good they provided you with the data rather than leave you dangling and your Dr. seems well connected for future trials. There's no doubt no-ifn or minimal-ifn tx is on its way. Given today's news it looks like waiting for it  is the right choice. Not great news, but it sure beats the disappointment of a failed attempt. All the best.

[susan400]

Okay, I'm back from my end of treatment visit.  I thought this was the last visit, but I still have to go back in 4 more weeks for post TX visit.  All SOC has stopped.  I took my last Riba this morning.  I was pretty much resigned to the fact that he would probably stop my treatment today, I had a feeling in my gut.  I have already accepted it and had already gone through my week of grieving and depression over it, so today was actually easier than I had anticipated.  I actually made it through w/o tears!

My interferon response totally S*cked!  It looks like I can really say with all certainty, I am a null responder. After 8 wks of TX (I had another one drawn this morning and won't have those results back for about a week or so), only about 1 log drop, TOTALLY unresponsive. Very disappointing.  I'm not mad at my doctor, I'm not mad at my study nurse, I'm not even mad at God, I am just plum mad at my dumb body!  There you go!.

My doctor was very nice and since he has alot of hands in the research pots (so to speak), he and some of his research colleagues are trying to get a trial set up for Protease Inhibitor failure patients, using hopefully the oral treatments and like a polymerase inhibitor.  I looked directly at him and said, 'just how long is this going to take, because I am tired of doing this and tired of these treatments interrupting my life.  I told him I had no intention of doing TX's when I am 60 yrs old'.   (10 yrs from now)  He told me that he thinks that they can get this trial in place for the Protease failure patients, probably within the next year or two.  He already has 3-4 (including me), protease failure patients-which actually surprised me a little.  Anyhow, I am going to try and not stay in sadville and pull on my happy hat...,  hopefully.    My mom is getting a knee replacement in another couple of weeks and I'm going to pay a visit to help my Dad out with her and get my mind on that, instead of this...     Thanks for all of your support.  If you want to see my roller coaster viral loads in the load conversion form.., I plotted them on my tracker here.    Susan400

[dointime]

"Still not a guarantee, but if Susan400s VL drop from lead in was strong enough (eg RVR or close it as was the case for Susansf)  the prospects looks good."

Susan400's tx history that she has been generous enough to share with us, is that in goodness knows how many previous tx's with SOC she has never reached UND.  So why would you think that she might suddenly be RVR or close this time?  

I'll wait for the evidence.
dointime

  

[willing]

>Did Susansf also have a history of having tx'ed already with a PI?

no, so there's definitely more risk for Susan400, but from all indications if her VL dropped fast enough during the past 9w that risk is  small:

- as several have pointed out there's plenty of data suggesting the PI-resistant variants selected by 5w of tela 4 years ago have largely been replaced by  PI-sensitive wild type

- the combination of a strong ifn response and triple tx is better than homegrown tomatoes: from available data for relapsers and naives,  SVR odds are in the high 80s/90s.

- in particular, a strong ifn response will trump even high baseline incidence of native PI-resistant variants, as shown in a recent post from frijole's

Still not a guarantee, but if Susan400s VL drop from lead in was strong enough (eg RVR or close it as was the case for Susansf)  the prospects looks good.

[meakea]

Susan, I wish you the best today!!   I'm sooo sorry about all the crapola you have been through over the years...I truly am.  Sitting here shaking my head.  There has to be a turn around for you one of these days and I'm hoping today is that day...with all GREAT news.  Keep us posted.  I truly admire you, by the way!

[paen53]

Good luck today, Susan. Hope you'll get the answers you need and deserve and some options for the future should you decide to move in that direction again.

Pam

[dointime]

"Susansf as I understand it, was in your same trial, also SOC only, and was able to continue onto boce with confidence because of her known very good VL drop before the PI. You should have the same option, if you choose to go that route."

Did Susansf also have a history of having tx'ed already with a PI?

dointime

[willing]

good luck tomorrow. It seems a great time to bring up that if they are genuinely sorry the trial didn't work out they will  make your VL drop over the past 9w quickly  available so you can evaluate alternatives.  Susansf as I understand it, was in your same trial, also SOC only, and was able to continue onto boce with confidence because of her known very good VL drop before the PI. You should have the same option, if you choose to go that route.

[elpasolady]

Good luck tomorrow, Susan.  You, indeed, have my sympathies, to say the least.  I will pray for you!!
I just want to add this......With the exception of maybe the first year that I learned I had HCV in 1996...( I know i contracted this 33 years ago in 1978)  I have pretty much lived my life in denial of having this disease. I know we are all made up differently, but as long as I went in to get my blood work checked from time to time, and the results were good, I did not worry. There was a period that I did not get checked for 3 years...it was that far from my mind.  I am not saying I was wise, but that's just how it was for me.  The only reason I am treating now, is because of the new drugs and because we now have health insurance, which may not be the case in the very near future. If it were not for the health insurance issue, I may still have waited.  I have not been sick a day from HCV thus far.  I don't know your history, or your levels  but If you are a stage 1-2, I would tell you to just put this on the back shelf, live your life as if you don't have this, (of course, be careful and take care of yourself) Your diet and exercise can do much to keep this at bay. You seem to do so much  meaningful work when you are not consumed with your TX.  Keep that focus, and in a few years when they really come up with a better treatment and cure for Hep C, you can try again.  Without the horrible side effects they are trying so hard to do away with, you will have nothing to lose to try again in the future.  
Don't forget...you are NOT your HCV.  You are so much more than this!!!  Don't let it consume your thoughts.  It is a part of you, that for now, may just need to die, in your mind, at least.
I  just wanted to try to give you a different perspective, for what it's worth!  You are not a failure, it is just not  your time.
Please keep in touch and I want to give you a BIG HUG!  
Debbie

[flcyclist]

Susan, you certainly haven't gone over the top considering your situation.  And have done a good job of explaining exactly where you're at.  Wish you the best at your trial visit and choosing the next step.  

[susan400]

No worries.  Thanks for all of your support everybody.  Now I just will do my visit to trial site tomorrow and whatever happens, I'll go from there.  I appreciate all of you letting me rale, and rant and rave, and b*tch.  I know I've gone over the top.  I am TRYING to pull positive up out of my gut.  Susan400

[pommes]

I apologize too!    It's so easy for other people to spout off about what to do, and especially to tell you what not to do.    I haven't even treated, so how can I possibly appreciate the enormity of what you're dealing with.

I didn't want you to get the wrong impression that your doctor is behind-the-times, or that there was an obviously good route for you to take.    You've had it so tough and it's not clear how things are going to get better right way.

Sounds like you are living a total nightmare, despite doing everything you possibly could do.    You got every reason to be sick and tired.

Kudos to you, warrior woman.

renata  

[lynda607]

It is your body and mind Susan and you must do what you must to heal.  Life goes on, whether we're living with or without HCV.

I apologize if my posts upset you, I was trying to point out that there is no concrete data showing re-treatment with a PI after a certain amount of time is off the table but because you feel the way you do it is a moot point so no sense beating a dead horse.

Good luck and I agree, at some point we have to stop the HCV madness.  Please don't be too hard on yourself for past mistakes, we eventually get to where we want to be because of where we've been before.    

[susan400]

Once again, Boceprevir/Victrelis is off the table, as I said above, so this part of the conversation is a moot point.  As far as letting my body rest and waiting..., I'm sick and tired of waiting. I had to wait 3 yrs for this darn treatment to materialize.  Waiting is all I've been doing and I'm tired of it.  I want to forget about the dumb disease and just pretend like I don't have it.  Walking around with having this in my body just reminds reminds me of my past, which I want to forget and want to be able to move forward with my life.  Kind of hard to do when I have to keep on hearing about coming in for the liver labs and sono's and blah, blah, blah.  Every time I hear about it, it brings up all of the horrible mistakes that I made in my past, and how I got this to begin with.  I want this nasty disease to be gone.  And waiting for the perfect treatment and/or the right combination of drugs, is a laugh as well.  That may never happen for me since I have Prot.Resist.  There are no guarantees w/TX in my body, with this disease.  At this point, as far as I'm concerned they are all a slim chance.  Now the Hep C vaccine, that's an interesting thing that being worked on.  If it would actually cure an active chronic Hep C, that would be something worthwhile.  They came out with a vaccine for melanoma, I heard, or maybe it's still in trials?  And that was supposed to actually cure some forms of melanoma.  

Susan400

[lynda607]

I am not saying resistant variants are not an issue for everyone or do not exist after 3 years, but there is data showing a definite decrease over time.  Susan had very little exposure to Telaprevir which is also a plus.

http://pi.vrtx.com/files/uspi_telaprevir.pdf

Persistence of Resistance-Associated Substitutions
Persistence of telaprevir-resistant NS3 amino acid substitutions has been observed following treatment failure. Of a combined 255 treatment-naïve and
previously treated subjects from Studies 108, 111, and C216 in whom telaprevir-resistant variants had emerged during treatment, 103 (40%) had detectable
resistant variants by population sequencing at end of study (follow-up range 2-70 weeks, median 45 weeks) and results for loss of variants were similar
across the three studies. In the combined studies, 46% of the telaprevir-resistant substitutions in subtype 1a and 16% of the substitutions in subtype 1b were
still detected by the end of study: 29% of V36, 16% of T54, 38% of R155, 14% of A156, and 44% of V36M+R155K variants were detected at the end of
study.
In a 3-year follow-up study of 56 treatment-naïve and prior treatment-failure subjects who did not achieve SVR with a telaprevir regimen in a Phase 2 study
and had telaprevir-resistant variants after treatment failure, variants were detected by population sequencing in 11% (6/56) of subjects (median follow-up of
25 months). Telaprevir-resistant variants V36L/M, T54S, and R155K were detectable (present at greater than 25% of the viral population) in some subjects
at 24 months. By 36 months, V36M, T54A/S, and A156N/S/T variants had fallen below the level of detection by population sequencing in all subjects. At
36 months, 3% of the subject isolates that had the R155K variant still had detectable R155K variants by population sequencing.
The lack of detection of a substitution based on a population-based assay does not necessarily indicate the substitution has declined to the pre-treatment
level. The long-term clinical impact of the emergence or persistence of detectable INCIVEK resistance-associated substitutions is unknown. No data are
available regarding INCIVEK efficacy among patients who were previously exposed to INCIVEK, or who previously failed treatment with an INCIVEKcontaining
regimen.

[lynda607]

http://www.natap.org/2010/AASLD/AASLD_66.htm

http://www.hivandhepatitis.com/2010_conference/aasld/docs/1123_a.html

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2893.2011.01449.x/abstract

http://www.natap.org/2010/EASL/EASL_07.htm

[pommes]

I agree with the last post.    Trust your doctor, wait for a better treatment.

The research Lynda605 points to strongly suggests that resistance is not an issue for re-treatment with some protease inhibitors.    Even so, why do it?   It is after all just RESEARCH thus far, and as dointim points out, even if the resistant variants have declined, re-treatment with the protease inhibitor may or may not be effective.   And why treat with something that may have serious even if unlikely resistance issues (the paper from Lynda607 mentions limitations to detection of resistant variants, and dire consequences of misestimating) when there are better options coming down the line?

After all these horrific treatment experiences, you must be emotionally and physically exhausted.    Your liver is still relatively healthy---no need to rush to sign up to be lab rat yet again.    Rest and wait for the Right Stuff.

But do push on that IL28b testing (no excuse for your doctor's office to delay on that).

Take care,
renata

p.s.  Lynda607 I do thank you for pointing us to that set of slides.    Definite eye-opener, and good wake-up call for me to realize how easily I can be duped into swallowing conventional wisdom (like the "obvious" cross-resistance issues of PTIs).   And whoa big relief to see public acknowledgment of worries about what will happen when all these new drug treatments land in the lap of our Happy Hepatologists.

[dointime]

lynda607 - the study that you posted does not say at all that resistance should not be an issue after 3 years.  I really don't know where you get that from.  

susan400 - on the basis that you may still have resistant mutations which would make the boc ineffective, and that SOC alone will not do it for you, I'm with your doc on this one.  Even if the boc would work, what would be your realistic chances based on your ifn response?  If I were you I'd trust your doc and not what you hear on this board.  The guy knows what he is doing and he'll get you there.  You have the liver time, you just need the patience.      

dointime
------------------------------  
http://www.natap.org/2011/EASL/EASL_54.htm

"This is a controversial issue & was at this just completed EASL. Where a number of researchers said flatly 'we will be able to re-use HCV protease inhibitors after patients develop resistance if we wait 2 years for the mutations to disappear & this was pretty much said with regards to telaprevir following the oral presentation by Sullivan of Vertex reporting that mutations mostly disappear after 1.5 years following stopping telaprevir therapy'. This may end up being true but right now this is just a theory without any evidence, no data to support this supposition, it cannot be considered true until a study or real clinical evidence supports this. Until we have data on this question one cannot say flatly patients will be able to re-use a HCV protease after resistance and receive viral load reductions from the drug. Will such a study ever be done, I don't know. There are many other classes of HCV drugs in development so in the future patients ought to be able to switch to a regimen of 2-4 oral drugs with or without peg/rbv without a protease, so the question may be moot. Still I think we need to clarify this. One issue is that the Sullivan study did not use ultra-deep sequencing, which in this study below shows mutations missed by clonal sequencing are picked up by UDS. At baseline before therapy mutations pre-exist, so 2 years later you would expect these same pre-existing mutations to be present but HCV multi-drug therapy suppresses these mutations and SVR still has been achieved evidenced by the studies with telaprevir & boceprevir, but the question is will these mutations be further enriched after failing therapy, will mutations accumulate to a significant degree if a patient remains on failing therapy, will compensatory mutations accumulate, and will these situations persist & affect re-treatment with a PI, I don't know the answer to these questions and I don't think anyone does. Perhaps the prediction that this will not be a problem is correct but we don't know & we have not studied this adequately.

[susan400]

I don't know how to argue this point with a top of the line highly educationed hepatologist Professor Dr.  I barely graduated from H.S. with a H.S. diploma.  I do well do have fairly intelligent conversations with most doctor's concerning my disease, but to question his opinion, I'm not sure that I could hold my own in that argument.  All I did so far was beg for him to right the script and I was told NO, he would not do it, because he said it was not in my best interest.

Susan400

[willbb]

http://hepatitiscnewdrugs.blogspot.com/search/label/protease%20inhibitor-%20%28NS3%2F4A%29%20Drug%20Resistance%20Test

[lynda607]

http://www.informedhorizons.com/resistance2011/pdf/Wyles.pdf

http://www.natap.org/2011/EASL/EASL_54.htm


Labcorp offers this test but I do not know if it is used to determine resistance profile for those previously treated with a DAA.

Hepatitis C Virus (HCV), Quantitative, RNA PCR (Graphical) With Reflex to Hepatitis C Virus (HCV) GenoSure® NS3/4A.  Test #550066

If you access the Labcorp test menu and find that particular test you can also click on the link they provide "Related Documents: Hepatitis C Virus (HCV) Resistance Testing: Applying the Model of HIV Drug Resistance Monitoring" which gives additional info.