NEW YORK (GenomeWeb News) – The National Cancer Institute said today that it has launched a pilot study this month that will assess the clinical utility of treating cancer patients based on known pharmacogenetic mutations versus standard care.
In the study, called the Molecular Profiling based Assignment of Cancer Therapeutics, or M-PACT, researchers will sequence the tumors of hundreds of patients for 391 different mutations in 20 genes known in the literature to impact response to various targeted therapies. Based on the genetic profile of screened patients, investigators hope to enroll nearly 200 study participants with solid tumors who are resistant to standard therapy.
The aim of the prospective, randomized study is to determine the degree to which cancer patients will benefit from treatments administered according to single pharmacogenetic mutations, compared to treatments given using non-genetic strategies.
"Patients will have their tumors genetically screened and if a pre-defined mutation is found, they will receive treatment with targeted agents," Shivaani Kummar, head of NCI’s developmental therapeutics clinic and the principal investigator of M-PACT, said in a statement. "What we don’t know, however, is whether using this approach to assign targeted treatments is really effective at providing clinical benefit to patients, as most tumors have multiple mutations and it’s not always clear which mutation to target and which agent is most likely to provide maximal benefit."
Additionally, researchers hope to identify patient subgroups that are most likely to benefit from certain kinds of treatments, in the hopes that this knowledge will speed development of newer oncologics by spurring smaller, more efficient, and cheaper clinical trials.
Patients in M-PACT will be randomized into two treatment arms and receive one of four therapeutic regimens. In one arm, patients will receive treatments based on the specific mutation or pathway implicated in their disease, and in the comparator arm participants will receive treatment that is not pharmacogenetically guided. If patients in the comparator arm progress on therapy, they will have the option to cross over to the pharmacogenetically guided treatment arm.
Researchers will use in the study a US Food and Drug Administration evaluated molecular sequencing protocol for tumor biopsy samples. Additionally, in order to be eligible for M-PACT, study participants with known driver mutations must have already received drugs targeting that mutation. For example, melanoma patients with V600E BRAF mutations must have received a BRAF inhibitor, and non-small cell lung cancer patients with ALK or EGFR mutations should have been treated with agents that target those markers.
NCI highlighted that M-PACT is one of the first studies to employ a randomized trial design to gauge if pharmacogenetic testing can improve the rate and duration of cancer therapy response in patients.
M-PACT is currently open for patient enrollment and researchers hope to report results from the trial by 2017. Although the study will initially be launched at NCI, the institute will eventually open it up to researchers in its Early Therapeutics Clinical Trials Network.
"We … believe that M-PACT can be a model for trials nationwide, particularly those that employ genetically driven treatment selection approaches in their design," James Doroshow, NCI deputy director for clinical and translational research, said in a statement.