RE:RE:RE:RE:RE:Interview with Dr. Shah I am hoping they would announce more details as the trial progresses for instance each escalation sequence and results etc.… I am not a clinical trial expert so I asked Spartrap about the timing going forward, it seems ideally(if everything goes fine) it can take about 6 months before a good number(highest possible dosage with no adverse effects as per planned) for the MTD is known so the longer it takes the better if they choose to announce the final result(which at the time they definitely should issue a PR with all the details which is the bare minimum of information they should share with the investors/market imo) that’s why I believe they also should feed the market with any progress along the process.
This was Spartrap’s response and after that some information about traditional 3+3 escalation design.
“well if it's a classic 3+3 escalation design as I suppose, you have cohorts of 3 pts per dose, and they continue on that dose up to the end until toxicity or other withdrawal (so, one cycle every 3 weeks, following the usual docetaxel posology). After the first cycle, a new cohort of 3 pts is started, either at the next dose or at the same dose if there was a toxicity observed in the previous level. There might be a few days of delay between the assessment of cohort 1 and starting of cohort 2, depending on trial organization, availability of pts, etc. So here we have 7 doses to test. 30, 60, 120 and then 4 Fibonacci. In the ideal case where no toxicity is found, we will end up with 7 cohorts treated with at least one cycle in a time span of, say, (21+2)*7=161 days (5.5 months)”
“Traditional 3+3 Design
The traditional 3+3 design remains the prevailing method for conducting phase I cancer clinical trials (7). It requires no modeling of the dose–toxicity curve beyond the classical assumption for cytotoxic drugs that toxicity increases with dose. This rule-based design proceeds with cohorts of three patients; the first cohort is treated at a starting dose that is considered to be safe based on extrapolation from animal toxicological data, and the subsequent cohorts are treated at increasing dose levels that have been fixed in advance (Figure 2, B). Historically, dose escalation has followed a modified Fibonacci sequence in which the dose increments become smaller as the dose increases (eg, the dose first increases by 100% of the preceding dose, and thereafter by 67%, 50%, 40%, and 30%–35% of the preceding doses). In most cases, the prespecified dose levels do not fit the exact Fibonacci sequence as described in the 12th century (5). If none of the three patients in a cohort experiences a dose-limiting toxicity, another three patients will be treated at the next higher dose level. However, if one of the first three patients experiences a dose-limiting toxicity, three more patients will be treated at the same dose level. The dose escalation continues until at least two patients among a cohort of three to six patients experience dose-limiting toxicities (ie, ≥33% of patients with a dose-limiting toxicity at that dose level). The recommended dose for phase II trials is conventionally defined as the dose level just below this toxic dose level.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684552/
palinc2000 wrote: Very interesting interview!
Will there be a PR or similar when the MTD will have been determined and will they share what the actual dose will be?