Therapeutic oncology vaccines have risen in prominence in recent years, prompting increased interest from contract research organisations (CRO), notably Encorium that is specialising in the field.
In response the US Food and Drug Administration (FDA) has issued draft guidance on how to conduct clinical trials of cancer vaccines, which have a different mode of action than other oncology treatments and consequently require special considerations.
These differences impact directly on patient selection. Trials of conventional treatments recruit patients with advanced metastatic diseases that progress quickly, allowing sites to enrol, dose and evaluate in a reasonably short period of time.
However, this model might not be effective at evaluating cancer vaccines. Unlike cytotoxic agents the impact of cancer vaccines may not be apparent after a short period of time because the anti-tumour immune response needs to develop.
Furthermore, patients with advanced metastatic diseases have usually received multiple treatments and this can reduce the effectiveness of their immune system and consequently the cancer vaccine as well.
These factors lead the FDA to recommend “testing cancer vaccines in patients with no evidence of residual disease or minimal burden of disease” but this will increase development time. Trial designers must assess the pros and cons of recruiting patients from this group.
Early stage trials
The patient recruitment considerations impact on both early and late stage clinical trials but the guidance also makes recommendations specific to each developmental period.
Dose escalation is a primary consideration of early stage research but the FDA believes previous cancer vaccine trials may have used an inappropriate design.
Cancer therapeutics generally use the 3+3 design but when applied to vaccines it has often failed to establish the maximum tolerated dose (MTD).
Considering this, and the relatively tolerable safety profile of some cancer vaccines, the guidance recommends using alternative dose escalation approaches such as accelerated titration.
The complete draft guidance can be viewed here.