RE:RE:Urocidin Next Clinical Trial ProtocolHT, I would be prepared to change my mind on Papillary. Maybe it won't be randomized with a placebo as the comparator arm. Yes, it could very well be a single arm trial. The discussion mentioned a number of key points on this issue:
- "Low-Risk Papillary" is not nearly as lethal as CIS. Going into the trial, the papillary cancer is absent, meaning it got removed by the TURBT. You know your drug failed when the papillary tumor grows back or comes back as CIS. Then you treat it again. Low-Risk Papillary doesn't normally go straight to muscle-invasive, which is lethal.
- CIS patients on the other hand enter the trial with cancer intact. You know you succeeded when you manage to shrink or eliminate the tumor. But since the next progression is muscle-invasive, putting someone on a placebo is a likely death sentence. That is unethical and would not be allowed by the FDA.
- Hence, for a Low-Risk Papillary trial, a placebo could be allowed as a control arm from an ethical standpoint.
- However, I agree with you that doctors who own the patient would be reluctant to sign up for something that would result in "no treatment". The forum talked about how doctors have treatment approaches that they are comfortable with and don't necessarily adopt FDA-approved therapies. Much less take chances on a trial.
- The panel did talk about the importance of making it easy to recruit patients to the trial since BCG-refractory bladder cancer is a relatively rare disease. One panelist started discussing a rigorous academic issue about trial design, but the FDA person basically said we have to be practical. If the design makes it too hard to recruit patients then no company can afford to run the trial and the companies won't bother launching any trials. Then we won't have any new drugs after several decades, which is the problem we have now with Bladder Cancer.
- The panel did discuss that there is already enough data on BCG results from other completed trials over the past few decades that you could refer to those for the comparator data if you ran a single arm trial. That would likely be acceptable to the FDA.
- However, I do not have a good feel for what effects you would gather up with a placebo arm (practitioner bias, gender, geographic bias etc). I also don't know how clean the data is on a "do nothing" treatment from previous studies. What information do you forego by not doing a placebo arm? Is it worth enough to do it? I don't know.
Overall, yes, a Low-Risk Papillary BCG-refractory trial could be single arm, immediate instillation, accelerated path, orphan drug. Single arm is an important issue because it cuts the cost of the trial in half and increases the speed of recruitment ("accrual" in the vernacular of the participants in the discussion panel).
The good news is Bioniche scientists and FDA scientists will make the decision, not me.