RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:The other two clinics I've never heard of the situation that the presence or absence of a drug target significantly changes the dynamics of the drug from a toxicity point of view. I've always assumed that only a small proportion of the drug actually interacts with the tumour, most circulates in the blood and is (rapidly) eliminated without ever engaging with the tumour. The presence or absence of a SORT+ tumour doesn't change things all that much.
If any of what is being said here was true then pre-screening for sort+ tumour would be essential and they would be doing it. Searching for a MTD would be meaningless because effectively you would have two populations with two different MTDs.
I just don't think anything that is being said here can be true.
realitycheck4u wrote: Isn't this rather dangerous to do a trial where the patient has not been pre-screened for Sortilin then??
And if there is not sortilin to attract the PDC then what happens to the payload. Does it release anyhow
juniper88 wrote: I would think that if the Peptide cannot hone in to a sortilin receptor then eventually it would break down and the payload is release into the blood stream, similar to getting just a Taxol IV. My wife has had 11 cycles of taxol, which is very toxic. Taxol IV requires premeds, for example IV Benadryl because allergic reactions to Taxol can occur. Also, the IV is put in on a graduated basis. So, they start very slow and monitor the patient very closely. If nothing happens after 15 minutes the nurse increase the IV speed until eventually full speed is reached.
From my understanding, in the TH1902 trial there are no premeds and the IV is done at full speed. At a higher dose, if the peptide does not work I imagine you would find out rather quickly.
Also, Taxol is one of the Chemos that causes your hair to fall out (not all chemos do, my wife current treatment Carboplatin with Caelyx has allowed her to keep all her hair.) So, even the patient should be able to notice if TH1902 is working with out any bloodwork. The hair start falling between the 2nd and 3rd week after the treatment.
scarlet1967 wrote: Yes .
realitycheck4u wrote: So if the patient does not have any sortilin receptors in their cancer (which is obvious for many patients) then the Sort1+ technology will not find the cancer cell (no receptor to attract it) - and it will not release its payload there. Right?
Does this mean it therefore not work for the patient?
And if there is not sortilin to attract the PDC then what happens to the payload. Does it release anyhow and there be too toxic and they are testing dosage of the Drug payload far beyond what is typically allowed.
qwerty22 wrote:
I don't think you have it quite right, I must admit it's confusing though. I think at each dose cycle they are recruiting new patients, +1 for the first 3 doses then +3-6 from dose 4 onwards. If they don't get toxicity they just keep moving up to the next higher dose adding new patients. If there are toxicity signs then it gets more complicated. Depending on the severity of the toxicity and the number of patients with toxicity they might continue up to next dose, pause at that dose and add more patients or decide they've reached the MTD. Toxicity is assessed in the first cycle of treatment for each patient. Patients keep getting cycles of the drug until their cancer progresses.
I think you are right to say if there is only mild toxicity signs then dose escalation is complete by late July but all the patients for that part will have been recruited by then. If there are grade 2 or 3 toxicities different rules apply and the trial might recruit more patients at the same dose so it takes longer to get to the end.
scarlet1967 wrote: If they are applying the modified accelerated dose escalation(speeding up the trial and not exposing extra patients unnecessarily to low dosage of the drug) with no sign of toxicity by now the first patient should have reached the third dose level of 120 mg/m2, as for Spartrap if they keep going with no toxicity they could reach a maximum dosage of 560 mg/m2 by end of July which is well above the therapeutic level and the ideal(but not highly likely) scenario failing that if and when toxicity is shown they will use a dosage slightly below the MTD for the first patient and start the 3+3 conventional design trial on patients with the data in hand. The only problem again based on what has been said elsewhere is if the first patient had sort1 negative cancer when they try it on sort1 positive patients they could possibly show severe adverse symptoms. I agree these well-established centers which are running multiple trials probably won’t be as enthusiastic as the Gettysburg clinic re the results one can only hope the company feed the market if and when the results are positive.
Wino115 wrote: I'm still curious if we're just at 1 patient or there's more. Given those clinics are huge and well-known centers doing hundreds of trials, I doubt we'll see the level of excitement expressed by good Dr. Shah in Gettysburg. Hopefully we get a follow-up from them or the local paper in a few months.
scarlet1967 wrote: That's correct if you go to their main website and search for clinical trials then choose cancer you get to the link I posted earlier. They have many locations I believe that link possibly shows the trials for all the locations.
Wino115 wrote: Isn't Cedars Sinai in LA the third?
scarlet1967 wrote: I will be delighted if you or anyone else beat me re good news:)
Hopefully the company itself start communicating the good news more often on well followed platforms.
qwerty22 wrote: I've been doing the same.
It annoyed me that you beat me to seeing the trial appear on the md Anderson website :)
scarlet1967 wrote:
Cancer
Cancer
Find a Karmanos Clinical Trial
These are the other two cancer clinics although it’s early in the process I periodically check their site in case TH1902 shows up.
Both centres seem to be well resourced.