A Tisket a Tasket…Trials Now Come in “Baskets”

Elly Cohen, PhD, program director of BreastCancerTrials.org, wrote this post for Breast Cancer Clinical Trials Matter to You about a recent innovation in cancer research: basket trials.

Basket trials (also known as bucket trials) are a new category of clinical trials that demonstrate the emerging importance of precision medicine in cancer care. They are distinguished from traditional clinical trials in that they enroll patients across multiple cancer types by focusing on a tumor’s mutation status rather than its primary site of origin. Basket trials are made possible by our rapidly accruing knowledge about molecular pathways regulating cell growth, cancer-producing mutations to these pathways, and therapies that target these mutations.

“NCI-MPACT: Molecular Profiling-Based Assignment of Cancer Therapy for Patients With Advanced Solid Tumors” is an example of a basket trial that is open to patients with breast cancer and other solid tumors that have progressed on prior therapy. As is typical of a basket trial, patients are first evaluated in a screening phase during which time their tumors are sent to a laboratory for genetic sequencing. Only patients with one of the four mutations under study in NCI-MPACT continue to the treatment phase of the study. After an additional eligibility review, patients are grouped by mutation status and within each group, randomized to receive either a targeted or a non-targeted therapy. In NCI-MPACT, four different mutation/targeted therapy combinations are being studied.

The NCI-MATCH (Molecular Analysis for Therapy Choice) trial is another basket study enrolling breast cancer patients. Initially opened in mid-August 2015 with 10 treatment groups, its accrual far exceeded expectations. This caused delays in tumor testing that impeded the flow of patients from screening to treatment. NCI-MATCH re-opened for patient enrollment to its screening phase in May 2016 after being temporarily closed for an interim analysis. The reopened trial will expand to 24 arms and is expected to enroll 5000 patients at 796 sites across the country. To address screening delays, investigators will add laboratory resources to reduce the bottleneck between screening and treatment. To learn more about NCI-MATCH, go to cancer.gov/nci-match.

As is the case with NCI-Match, an important benefit to the basket cell design is that it allows investigators to include patients with uncommon cancer types in clinical trials if they share common mutations. This will become increasingly more important as patients, even those with breast cancer or other prevalent solid tumors, become increasingly subdivided by mutation status. Without the basket trials, the resulting patient populations might be too small to determine meaningful outcomes within traditional randomized clinical trials.

Given the excitement and interest in basket trials, it’s hard to believe that the first publication of a basket study appeared in the New England Journal of Medicine in August 2015. Conducted by investigators at Memorial Sloan-Kettering, it evaluated vemurafenib, a drug that had been proven to treat BRAFV600-mutated melanoma tumors, in non-melanoma tumors with a BRAFV600 mutation. People with lung, colorectal, and ovarian cancers as well as those with rare diseases, such as Erdheim-Chester disease were included in the study. The study showed effectivness of vemurafenib for lung cancer and Erdehim-Chester, but more importantly, established the basket trials concept as a new and important model of clinical trial design.

Currently, basket trials are only available for patients with metastatic cancer.If you are interested in learning more about basket trials, BreastCancerTrials.org has an updated list of basket trials that are registered in ClinicalTrials.gov or Cancer.gov and actively recruiting breast cancer patients. If you contact a research site, you may want to inquire about the time you might expect to wait between the screening and treatment phases of the trial.

In summary, basket trials offer a new and exciting way to evaluate targeted therapies across cancers and to accelerate their availability in the clinic.  By focusing on the genetic properties of tumors, they will help to make precision medicine a reality for patients in cancer care.

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