Home Forums Melanoma Diagnosis: Stage IV Everything you want to know about the expanded access of PD1 Reply To: Everything you want to know about the expanded access of PD1

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PhillyRed
Participant

The reason that most early phase cancer trials exclude patients with active central nervous system metastases has to do with the need for establishing a toxicity profile for the investigational agent, not based on the presumptions that it will or will not gain access to the brain/central nervous system (due to the blood-brain barrier), or whether or not it will be effective against brain mets. As mandated by the FDA, a complete toxicity profile of the investigational agent for all the organ systems of the body (including the central nervous system) must be determined before the agent is granted approval. Because central nervous system mets frequently present with a variety of neurological symptoms (depending on the size, location, and parts of the brain affected by the tumor), they can interfere with determining whether or not the investigational agent itself causes neurological adverse events, which may be serious health risks. Some early phase trials get around excluding patients with active brain mets by allowing enrollment of patients with stable brain mets (ie, causing no neurological symptoms for a certain length of time, eg, 2-3 months, or mets that have not shown growth on scans for a length of time). It depends on the pharmaceutical company, the expected toxicity profile of the particular investigational agent, and communications with the FDA about whether or not the brain mets should be allowed. Often, as the investigational agent moves into later phase trials and the company and FDA have more accumulated safety data from the earlier trials and have a better understanding of the toxicity profile, the restrictions against brain mets are relaxed, and patients with brain mets may be able to take part in the trials. With respect to the expanded access program, I think that the brain mets are being excluded because they are allowing additional patients, outside of the trial, to be able to take the drug, even though at this point in time, they don’t have extensive safety yet (as they would for a later trial), but they consider that the potential benefits of the drug for the patients outweigh the potential risks.