Gone for good.
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The corporate fact sheet dated Sept 12 had the results of the second-line NSCLC trial as announced at the Chicago symposium.
So I guess they had to remove that info until that matter has been cleared up, one way or another.
Bungler, I agree with you. I don't think the trial data was violated and the double-blind was not broken.
No one knew about any of this until the last 3 weeks at most when the data was being given a complete
going over in preparation for the meeting with FDA. Even if some of the data couldn't be used and the statistical
significance of the pooled data was reduced there is no requirement from the FDA that you have to have
statistically significant data to start a phase 3. If that were true very few phase 3 trials would have been done.
I also feel that the independent monitoring board saw that the two treatment arms were giving results so
alike at the time of unblinding they felt that it was statistically valid to do a pooled analysis. I don't think
they knew of the "problem" with the treatment arm samples and were trying to some how "fix" it.
Sorry, RRdog I am a free member and can't send private messages. But hold on I'll have someone else do it for me.
FTM
Mojojojo, could you send me a private message with an e-mail address? Thanks.
What is going on? Did someone just buy 10% of Peregrine?
I think you are referring to the first-line trial, not the second-line trial of NSCLC. This was a blinded trial so nobody
could have seen what was happening in real time. Today's PR specifically stated that this does not have any
effect on other ongoing trials, i.e. the first-line NSCLC trial. We do not know if the errors mixed the control arm
with the treatment arms. I assume that did not happen based on what was said in the PR.
When you call it a hoax you lose all credibility. It was Peregrine that called attention to the errors. If it was all a hoax why would they do that?
Mojojojo, any ideas on the trial problems and their effects?
I would expect there would only be small differences between the old pooled results and the new pooled results.
I think the company is obligated to report any problems, so you can't say this was for no reason. I don't
blame Peregrine for this. It is better the errors were found now than in 6 months just before the phase 3 was to launch.
Some more observations. If you assume that the 3 mg/kg dose will give better results than the 1 mg/kg dose
then it should show up it the results, and it does. The ORR, PFS, MOS for the 3 mg/kg arm are all better than
the 1 mg/kg arm. The safety results are pretty consistent with that idea also. If the two treatment arms were
totally mixed up then I would not expect to see such consistent differences between the two arms, instead they
would be much more similar. This says to me that the errors must have minor impact. In fact it could be
that when corrected the two treatment arms will become a little more different from each other.
I have been rereading the PR from today since that is all we have to go on right now. This is what I found useful.
Maybe RRdog just has better things to do, or maybe he will wait until more information is available.
He hasn't posted since Sept 18th.
http://investorshub.advfn.com/boards/profile.aspx?user=248331
Nobody is happy, we can all agree on that.
Sorry Loofman, but I feel that is exactly what they should be doing. I would hope that
by the time of the annual shareholders meeting they would have the answers.
If all three arms were mixed then the results should all be closer together. I still believe
the problems are with the assignment of the 1 mg/kg and 3 mg/kg doses and will do so
until the details are released. There could be more of a difference between the 1 mg
and 3 mg arms than previously presented, but we'll have to wait and see.
When all the facts come out.
I am. I think it just got more interesting.
Maybe someone who had shorted the stock?
I agree with your assessment. I am assuming that any error in dosage was done at the beginning and so
the same dose was used throughout the trial. If patients received 1 mg/kg one week and 3 mg/kg the next
week then I think the trial will have to be redone, but that still would give information as to whether bavi works or not.
Luckily this is not a phase 3 trial submitted for FDA approval. The decision to start phase 3 might not be affected. We'll see.
I am not so sure. If it was just a clerical error maybe not a broken protocol. The trial was still blinded, if the error
didn't change the randomization then it could be okay for moving to phase 3. The AA might not fly though.
At this point blaming this on foreign sites is not warranted. The error might have affected all sites or
just some here in the US, we just don't know yet. In any case it seems to be a problem with the contractor.
The trial sites just acted on the information given to them so there is no reason to blame this on them.
Obviously the patients are still dead or alive, the question to be answered is whether this error affects only
the two arms given bavi, or not. The fact that the 3 mg/kg dose arm was slightly better than the 1 mg/kg
arm is consistent with what was said about saturation expected at 1 mg/kg, so it is hard to see a major
problem with the dosing. If the problem was really big it should have been obvious already in the results
with one arm performing much better than the other.Likewise if patients who should have received placebo
got bavi instead, and vice versa, then you should see the results get closer together, not farther apart.
We just have to wait and see. I don't expect to hear anything more until everything is verified and checked,
and then a third party brought in to check it all.
I am sticking to my "best " interpretation for now, that it is a mix up in dosages for the two treatment arms.
If everything was totally mixed up then I would expect that all three arms would have about the same results.
If patients who only got placebo were assigned to one of the treatment arms how could you explain the big MOS values?
I think the mixing of the treatment arm dosages makes most sense for now. We'll see.
Could be there is a paper trail of the errors in assignment and so who got what dose can be resolved.
I am not prepared to say anything about how the statistics will come out. If the error does only affect
the two treatment arms then maybe this will come out okay. In any case the credibility of the
company will be a big issue. I still have confidence in all the preclinical data and the other trials done.
I wouldn't say that until everything is known and the results recalculated.
Felt like a kick in the stomach! Rereading the PR does give me some hope. It says the errors were
in the treatment group coding. To me that says the control arm was not affected and the control MOS
of 5.6 months is good. The best interpretation would be that the 1 mg/kg and 3 mg/kg arms were mixed up.
That could be which patients got which dosage. The PR says
"A subsequent review of information has determined that the source of these discrepancies appear to have been
associated with the independent third-party contracted to code and distribute investigational drug product."
So I expect the RR, PFS, MOS of the two treatment arms will all change.
Going forward some other independent group will be needed to check everything to give any credibility to the final results.
At this point hope is all we have.
New study on breast cancer mutations in today's NYT.
http://www.nytimes.com/2012/09/24/health/study-finds-variations-of-breast-cancer.html?ref=global-home
These types of study keep coming out with more and more details of the mutations involved with various
types of cancer. Each time it just reinforces the huge advantage that the MOA of bavituximab has over
the conventional approach of targeting each individual mutation. From today's NYT article.
....
"The study’s biggest surprise involved a particularly deadly breast cancer whose tumor cells resemble basal cells of the skin and sweat glands, which are present in the deepest layer of the skin. These breast basal cells form a scaffolding for milk duct cells. Such cancers are often called triple negative but the study researchers call them basal-like.
Basal-like cancers are most frequent in younger women, in African-Americans and in women with breast cancer genes BRCA1 and BRCA2.
And, the researchers report, their genetic derangements make these cancers a much closer kin of ovarian cancers than of other breast cancers. Basal-like breast cancers also resemble squamous cell cancer of the lung."
....
"For now, despite the tantalizing possibilities, patients will have to wait for clinical trials to see whether drugs that block the genetic aberrations can stop the cancers. And it could be a massive undertaking to get all the drug testing done. Because there are so many different ways a breast cancer cell can go awry, there may have to be dozens of drug studies, each focusing on a different genetic change.
...
There is no reason to expect that bavi would not be just as effective for basal-cell (triple negative) breast cancers,
ovarian cancer, and squamous cell lung cancer. Hopefully bavi will be used in clinical trails for these cancers in the future.
The dosing is weekly in these trials. The concentration of bavi needs to be maintained during treatment,
and I think the half-life (time to get to 50% of initial concentration) is about a week. If the patient enters monotherapy
with bavi it is still given weekly. They will have to do more studies to really know whether the monotherapy is
needed, or for how long, in those patients that continue to live. It could be that at some point these
patients have developed immunity to their cancer and so could stop, but all that is speculation for now. It was
shown in the rat study with glioma that 13% of them survived and had developed immunity.
The pancreatic trial is randomized, but open label, so it is known which patients get the bavi + GEM.
Extending the timeline is encouraging, but who knows how big an effect bavi will have on survival. This is
such a difficult cancer to treat that my optimism is tempered, but I said the same thing about second-line NSCLC.
More data on advanced pancreatic cancer trials. A new paper out.
Role of gemcitabine-based combination therapy in the management of advanced pancreatic cancer: A meta-analysis of randomised trials
European Journal of Cancer online Sept 16, 2012
http://www.sciencedirect.com/science/article/pii/S0959804912006818
Background
Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. Gemcitabine is the mainstay treatment for advanced disease. However, almost all up-to-date trials, that evaluated the benefit of gemcitabine-combination schedules, failed to demonstrate an improvement in overall survival (OS). In this study, we performed a systematic review and a meta-analysis of randomised clinical trials (RCTs) to investigate the efficacy and safety of gemcitabine-based combination regimens as compared to gemcitabine alone in the management of pancreatic cancer.
Findings: Thirty-four trials for a total of 10,660 patients were selected and included in the final
analysis. The analysis showed that combination chemotherapy confers benefit in terms of OS
(HR: 0.93; 95% confidence interval (CI): 0.89–0.97; p = 0.001).
Here is Table 1 from this paper showing 34 randomized trials. Every trial used GEM as the control arm,
and the combination treatment arms all used GEM + something.
Here I took the 32 with survival numbers and put them in a spreadsheet to calculate the mean
and standard deviation across the 32 trials. This gives us an idea of the variation across trials with
different patient groups and treatments added to GEM. It doesn't look too good. The treatment mean OS
is only 11% longer than the control mean. There are a few outliers. The two best are with the drug S-1.
If Bavi +GEM could double survival it would be a major improvement.
Jay has always been upfront with me and I respect him.
Who knows, maybe CS only wants the CEO to be there and King will be on a plane to ??? to sign some papers.
Ever heard of the internet? You think they didn't hear about it in Europe?
I just got the same thing from Jay Carlson.
As CJ pointed out here
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=79741219
the other abstract was not for a Roche sponsored trial and was not a test of Avastin but a Lily sponsored
trial of pemetrexed. Also, there is no way Peregrine could withdraw their abstract and replace it with
another one this late. At least you could get the facts straight, but then it wouldn't support your theory.
Hope not. Already bought my plane ticket and reserved a hotel room.