scarlet1967 wrote: So they start with lower dose arm if no or less than one DLT the higher dose arm will be the next step. The extra 3 months gives them plenty of time to determine BOTH efficacy and safety results. Traditionally as for efficacy they need back to back positive results from to consecutive dosing cycles however as the dosing are weekly one can only presume due to tight intervals most likely they will be looking for those results during the 3 months observation period. Also as per the document below the determination of efficacy in some cases can only be based on one clinical investigation' results, If I interpret it correctly?
My take is even if they get favourable results from first group they start the second group regardless in the hope of improving those results and if not based on the first group's results they can carry on to the next phase the expansion part(part 4).
Point is the trial is an ongoing learning process and ultimate RP2D could as well end up being 210mg/m2 if and when they get favourable results from that group and the second group end up having safety issue etc.
That's the way I understand this particular trial's design is aiming for.
"The amended study will be a modified 6+6 design with two different dosing regimens that are within the efficacious range for sudocetaxel zendusortide: 1.75 mg/kg on days 1, 8, and 15 of a 28-day cycle (similar to 210 mg/m2 every 3 weeks) and 2.5 mg/kg on the same schedule (similar to 300 mg/m2 every 3 weeks). A minimum of six patients will be enrolled at the 1.75 mg/kg dose followed by an observational period of three months to assess dose-limiting toxicity (DLT). If deemed safe (0 or 1 DLT), the trial will enroll an additional six patients at the 2.5 mg/kg dose. Following a second three-month observational period, four more patients will be enrolled at the higher dose, for a total of 16 patients in Part 3 of the trial."
https://www.fda.gov/media/71195/download
"The evidence needed to establish effectiveness is discussed in the guidance for industry Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products and the guidance for industry FDA Approval of New Cancer Treatment Uses for Marketed Drug and Biological Products. In many cases, at least two adequate and well-controlled clinical investigations are needed. In certain cases, evidence from a single adequate and well-controlled clinical investigation, with confirmatory evidence, can be sufficient (e.g., in cases in which a single multicenter study provides highly reliable and statistically strong evidence of an important clinical benefit). FDA may consider data from one adequate and well-controlled clinical investigation and confirmatory evidence as substantial evidence, if FDA determines that such data and evidence are sufficient to establish effectiveness.?
For example, for drugs approved for
treatment of patients with a specific stage of a particular malignancy, evidence from one adequate and well-controlled clinical investigation with confirmatory evidence may be sufficient to support an efficacy supplement for treatment of a different stage of the same cancer."