The U.S. Food and Drug Administration uses clinical trial results to determine whether to approve a new drug for marketing in the United States.

Clinical trials are designed to test the safety and efficacy of a drug or combination of drugs to treat a specific type of cancer, such as breast or lung cancer. Traditionally, early clinical trials are primarily focused on defining a safe dose of a drug. Later clinical trials are designed to determine the drug’s efficacy as well as longer term safety. If a drug is shown to be efficacious for one type of cancer, then new trials may be designed to see if the drug will work in other types of cancer. This process is called a sequential clinical trial design.

Patients with cancer from other sites of origin who might positively respond to the treatment are overlooked or studied in sequential trials, which may result in delayed access to a promising therapy. However, cancer genetic mutations and the therapies that target them permit genomic-based trials, which allow for innovative trial designs, including those known as basket trials and umbrella trials. The aim of these innovative clinical trial designs is to test and get safe and effective drugs to patients in a more efficient manner.

Basket Trials

Basket trials test the effect of a targeted agent on cancers with the same genetic mutation but of different origins. Patients with cancer caused by a shared genomic mutation, regardless of site of origin, are matched to an investigational therapy targeted to the mutation. This can increase the efficiency over the traditional, sequential method since patients with the same genetic mutation can be assessed under one trial even though they may have different sites of origin. For example, patients whose tumors all harbor a mutation in the BRAF gene could be studied under one clinical trial regardless of whether the type of cancer is melanoma or lung cancer. This approach can lead to more than one indication for a newly approved therapy, as opposed to just one indication at a time through the traditional, sequential approach.

Umbrella Trials

In contrast to basket trials, umbrella trials focus on a specific type of cancer. Umbrella trials test the effectiveness of multiple targeted agents across different genetic mutations in a single type of cancer. These trials facilitate screening and accrual into trials and have multiple, different arms under a single trial. A large number of patients with the same type of cancer can be screened for multiple genetic mutations and tested with different targeted therapies most likely to benefit them based on the genetic makeup of their cancer. For example, patients enrolled in an umbrella trial in lung cancer will be screened for a variety of mutations and will be assigned to different treatments based on the results of screening.