Advancements in genomics and precision medicine have led to the development of targeted therapies that address cancers based on their genetic mutations. Traditional Phase 1 to 3 clinical trials, which historically focused on tumor site of origin and histology, are evolving to target tumor-specific biomarkers, irrespective of tumor type. To address the challenges of investigating biomarkers within the current trial design, a new framework called the master protocol has emerged.
Master Protocol Framework
Master protocol refers to a single design developed to evaluate multiple hypotheses, improving efficiency and establishing uniformity based on the presence of specific biomarkers, rather than tumor types. This framework encompasses basket trials, umbrella trials, and platform trials.
Basket Trials
Basket trials assess the same treatment in several diseases or disease subtypes. These trials are mainly used in oncology and may involve patients with cancers affecting different organs but carrying the same alteration. Patients are enrolled based on the presence of a specific tumor biomarker, regardless of tumor type. The efficacy of the drug against the tumor biomarker is assessed, often in a single-arm study based on prior knowledge of the biomarker. Basket trials are particularly useful for rare cancer types but typically require confirmation with a larger trial for approval.
Umbrella Trials
Umbrella trials focus on a single tumor type with multiple different biomarkers. These trials assess the efficacy of multiple drugs, with patients receiving those that target their specific biomarker. Umbrella trials are used for cancers with different biomarkers, such as lung and breast cancer. They screen and enroll a greater number of patients based on multiple biomarkers, improving the possibility of benefits from targeted therapy. These trials require several study arms and must include many participants, with long-term and active follow-up.
Platform Trials
Platform trials evaluate multiple hypotheses in a single protocol. The design can be complicated, and the trials are typically randomized and without a termination date. They compare multiple arms simultaneously or one after the other. During the trial, arms can be added or discontinued according to trial rules, leading to a more rapid evaluation of drugs. Platform trials can modify drug dosage and sample size based on ongoing results but are difficult to perform due to the requirement of rapid and long-term follow-up. They also require complex statistical analyses.
These novel clinical trial formats offer survival advantages and allow for more inclusive enrollment of patients with cancer. Oncology nurses and other practitioners must carefully analyze the results and understand how to interpret the data and the design to effectively counsel patients and families.
