They described Phase 1 trials as a "union of laboratory and clinic", and discussed the development, testing, and approval process for new drugs. In Phase I trials, the primary outcomes are safety, tolerability, and finding the maximum dose of medication that can safely be given &mdash Treatment outcomes like tumor measurements are still secondary, but important. He said that he would give Phase II and III trials a higher priority because they are for medications that have already proven out in Phase I, but that patients need to think through what the control/comparison arm of the study is and whether that is something they are comfortable accepting. Some Phase II trials are open label (i.e., everyone receives the active medication), and that can be something to look for. They also mentioned that Phase I trials often have more lenient inclusion and exclusion criteria -- i.e., there will almost always be a Phase I trial a patient can qualify for, even if there are no Phase II or III trials that are a good fit. Within Phase I trials, the doctor said that those targeted to cancers like mine can be more worthwhile considering than those that are looking at a broad range of solid tumor types.
The doctor also said that I would be considered KRAS mutant from a trial eligibility perspective. While there may be some trials for KRAS mutants that restrict inclusion to those with the more common mutations, they believed that would be uncommon, and that I am the kind of patient that the average trial focused on refractory colorectal cancer in KRAS mutant patients. The one thing that may limit my trial eligibility is simply the number of protocols I have received already. They clarify that when trials specify an upper limit of the number of previous protocols received that I would count as having had three for that, and not four, as most trials would not count the Regorafenib since it is not a traditional cytotoxic protocol.
The doctor believes that the most promising trials for KRAS mutant refractory colorectal cancer right now are those with MEK inhibitors. They noted that there is also a MEK inhibitor (trametinib) that has recently been approved in the last month for melanoma. Their suggestion is that this medication could be an option for off-label use by me after Regorafenib stops working, especially if there are no Phase II or III trials that are a good fit at that time. They also said that while the immunotherapy trials are "intellectually cool and exciting", they are still very much a black box of unknowns, and it is much harder to predict potential benefits.
If I end up participating in a clinical trial at a remote site, my home hospital could potentially perform blood draws, but that other clinical monitoring would need to be done at the trial site. The doctor said that this would generally involve traveling to the trial site once or twice a month over the course of the study. They strongly encouraged the consideration of in-house studies at the NIH — both because they can be more "leading edge" because of their funding approach, and because they generally cover patient travel expenses. I definitely qualify as "scientifically interesting" at this point, due to both my increasingly lengthy survival with a relatively strong ECOG score (ie, apparent good health), and that this can be a plus in terms of getting into trials at places like the NIH.
(My thanks to