The Cleveland Clinic is beginning a study to assess the feasibility and clinical impact of using targeted sequencing, provided by Foundation Medicine, to guide cancer care for patients with a variety of solid tumors.
The effort intends to recruit 250 patients over one year who have advanced disease representing one of 15 solid tumor types associated with poor prognosis or relatively limited treatment options including colorectal cancers, pancreatic cancers, lung cancers, and triple-negative breast cancer among others.
Researchers — led by Davendra Sohal, a physician in the department of solid tumor oncology at the Cleveland Clinic's Taussig Cancer Institute — will collect samples, send them to Foundation Medicine for sequencing and analysis using the firm's 236-gene targeted sequencing test, and then review the results for potential therapeutic links and refer patients accordingly.
Sohal told Clinical Sequencing News this week that the group initially considered a variety of sequencing options through both commercial and academic partners when planning the study.
"We started exploring sequencing opportunities with academia, other universities' programs, and other commercial purveyors of such tests," Sohal said. "But we [homed] in on Foundation Medicine, which has an excellent platform and tests for [the full range] of genes known to be related to cancer."
According to Sohal, the team chose to focus on a subset of solid tumors in its study to limit the effort to areas where sequencing might have the greatest impact.
"We decided to look at diseases for which there are no great treatment options, but where we see enough patients to actually study this, and for which there is initial evidence that there are potential treatments that can be used and tested," he said.
The Cleveland Clinic will cover the costs of the study, from sample collection through sequencing and analysis, using internal funds, Sohal said.
Overall, the group is hoping to end the study with a sense of whether this type of a sequencing program would be feasible for the center in routine practice, and if so, whether it would have a positive impact on patients' health.
"Our first objective is just to see how well this can be performed in a routine setting," Sohal said. "We want to know how many specimens can be retrieved? How much tissue do we need? How much is the turnaround time?
"Then we need to look at, if we can do this, how does it actually help patients? So out of 250 patients, how many can get a [suggested] medicine based on the genomic results, and among those, how will that medicine actually affect their health?"
In considering the reports from Foundation Medicine's test — which will include mutation status as well as information about potential therapies associated with any detected mutations — Sohal said that the study leaders will consider referring patients for treatment with both FDA-approved drugs and to clinical trials of therapies in earlier development.
"There are many potential treatment options and we plan to explore them all," he said. "Number one is FDA-approved drugs. For example, with an EGFR mutation in lung cancer, we can offer erlotinib."
If no such targets are options, he said, the second category the team will consider will be off-label use of approved drugs, for example, treating with trastuzumab in a patient with HER2-mutated colon cancer.
Beyond that, the team will look for mutations that might be targeted by compounds in phase I, II, and III clinical trials.
By using Foundation Medicine's targeted sequencing service, the study will avoid some complications of other clinical sequencing trials because there will be less of a possibility that sequencing might turn up incidental or unexpected information about a patient's health or health risks.
However, Sohal said that as part of the consent process for the study, patients will be informed that there is a small possibility that the sequencing might uncover unanticipated information, for example, about the presence of an inherited cancer syndrome.
In about six months, Sohal said the group hopes to be able to do an interim analysis once about half of the patients have been enrolled to start to answer some of the study's feasibility questions. "Hopefully by then we will have updates on how things are looking," he said.
If the results of the study indicate that the testing strategy is feasible as a routine practice, Sohal said the group would plan to move toward offering it as a clinical service on an ongoing basis.
This would depend, however, on whether sequencing benefits patients within specific tumor types or across the board, he said.
"Let's say this is feasible, which we are working very hard to make sure," Sohal said. "If we prove that, yes, we can do this routinely, then we will need to see which, if any, patients this helped most."
"For example, if colorectal cancer patients benefit more, we might expand this just [for those] patients. But, if we find that it is a random scattering of patients who are helped with this, we could offer it as a routine test," he said.