Eligibility for Clinical Trials Based on Tumor Genotype

We are all accustomed to the idea that entry of a patient into a cancer clinical trial will usually be based on the histopathological diagnosis of the lesion, frequently supplemented by immunohistochemical (IHC) staining such as for estrogen and progesterone receptors. A recent blog note (see: Biospecimen Research: Use of “my” tissue?) got me thinking about a new research subject selection model that may take hold for entry into clinical trials. Below is an excerpt from the note which was written by Karl Schwartz, President of Patients Against Lymphoma:

Increasingly, eligibility for clinical trials will be determined not by the diagnosis, but by analysis of molecular features within the tumor that are targeted by new drugs. And so you may need viable fresh or fast-frozen tissue to participate in clinical trials, or to create personalized therapies already approved for use. That is, you may have important clinical reasons to transfer extra tissue stored following a biopsy, or donated to basic biospecimen research, for clinical uses. Below is a copy of our proposal that we hope provides a solution to a difficult policy issue: that of transfer of contributed biospecimens for unanticipated clinical uses, particularly for uses to determine eligibility in clinical trials.

Although this note relates in part to the issue of submission and storage of extra tumor tissue in biorepositories, it did get me thinking about a possible future scenario whereby initial entry into a clinical trial would be based on the genotype of a tumor rather than the histopathologic diagnosis. The current and most common model requires that  a patient, working in concert with an internist or surgeon, seeks entry into those clinical trials for which he or she meets the entry criteria, including the tissue diagnosis. The patient and physician initiates the transaction.

Let's turn this model around and think about an alternative approach. Tissue from a patient's newly discovered tumor would be genotyped in a hospital lab or reference lab and this information would then be submitted to a clearing house with the identify of the patient protected. The patient's clinical and tumor information would then be matched within this clearing house against open clinical trials seeking subjects with tumors meeting certain genotypic criteria. Offers to participate would then flow from the primary investigators of the open trials to the potential subjects. The time lag until definitive treatment would obviously be important so that this whole process would need to be expedited.

From my perspective, such an approach would have two major benefits. On the research side, the ideal subject could be recruited quickly depending, of course, on the volume of specimens passing through the clearing house. On the patient side, there is the potential that patients would be presented with more opportunities to participate in clinical trials than otherwise would occur and also, perhaps, to choose the optimal study among those offered to him or her. The definition of optimal here depends on the needs and wishes of the patient.

Comments

[Karl Schwartz]

It may be that the NCI biorepository model could also incorporate your idea, if the participating repositories focus on standardized *diagnostic* analysis ... In which case there sharing the analysis would be would be sufficient to determine eligibility in trials (no need to transfer tissue samples). Which speaks to the need to enable relinking of the biospecimen data with the patient in order to propose studies of interest - to serve translational research. As you know, in the hospital setting, it will be important that the storage and analysis be standardized in order to have confidence in the outcomes of subsequent trials. Doing so, I think, would be a way to partner with the National biospecimen network. See NCI Best Practices http://biospecimens.cancer.gov/practices/