As a newcomer to the biotech sector, I was hoping one of the regulars could answer this: I understand that there exists the potential to halt Comet-1 at the interim if the data meets certain metrics, but does potential for discontinuation also exist if the data is poor? Or does the trial continue regardless?
Thank you in advance
I hope Ernie corrects me if I'm wrong, but my impression is that there is a single planned interim analysis by the investigators as well as an independent committee constantly monitoring the trial. If the planned interim analysis doesn't meet the significance they allotted to it, the trial continues. However, at any time, the independent data monitoring committee can stop the trial if they deem it appropriate, and this can be for either excessive patient death or clear efficacy. See the article: "J&J Prostate Cancer Trial Shouldn’t Have Been Stopped Early."
"However, at any time, the independent data monitoring committee can stop the trial if they deem it appropriate, and this can be for either excessive patient death or clear efficacy."
You essentially have it right, but let's talk about this a bit. For the interim analysis the data monitoring committee is given a clear roadmap. The data will be run and if the pre-specified p value is attained, the trial is unblinded and presumably the company will submit an NDA. If the p value is not attained, the trial continues to the final analysis. Some analyses also include a futility analysis. Comet 1 does not. A futility analysis provides a path to discontinue a trial because it is unlikely to succeed if allowed to run to completion.
Beyond these boundaries, DBMC's have the discretion to recommend a trial be stopped for overwhelming efficacy or if they determine that the treatment is counterproductive and treatment arm patients are being harmed. Trial stoppage for overwhelming efficacy outside of an interim analysis is an incredibly rare event. However, just as "off-label" use is always overestimated on YMB's, there are always voices predicting early unblinding.
"COMET-1 is a randomized, double-blind, placebo-controlled trial designed to enroll 960 patients with mCRPC who have previously been treated with docetaxel, abiraterone acetate and/or enzalutamide. All patients in the trial have bone metastases and there is no limit to the number or type of prior treatments. Patients are randomized 2:1 to receive cabozantinib (60 mg daily) or prednisone (5 mg twice daily). The trial is event-driven and has 90% power to detect a 25% reduction in the risk of death (HR = 0.75) at the time of final analysis, which requires 578 events. A single interim analysis after 387 events is also planned and will assess if the trial achieved its primary endpoint; it will not include a futility analysis. The secondary endpoint of the trial is bone scan response as assessed by an independent radiology facility."