Conferees at the American Association of Cancer Research in March had the chance to hear about master clinical trial protocols from Marc Theoret, who is the Lead Medical Officer in the Office of Oncology Drug Products at CDER. Master clinical trial protocols is a concept promoted by the FDA in a draft guidance issued last September. The purpose of these protocols is to measure the effect of a single or combination of drugs in either a single cancer type or multiple cancer types in a trial with a single overall structure and multiple treatment arms. This would allow sponsors to expedite development by not requiring a separate protocol for every trial they plan to run. There are two types of specific designs discussed in the draft guidance:

1. Basket trials evaluate a single drug or drug combination in multiple disease subtypes
2. Umbrella trials evaluate multiple drugs or drug combination in a single disease subtype

More complex designs, including a combination of basket and umbrella designs, are mentioned but not discussed in detail.

While a master protocol allows for increased efficiency through a single approval process, shared control arm, and centralized data capture, there are challenges to the conduct and analysis of such trials that can present patient risk. The guidance discusses these challenges and naturally encourages discussion with the FDA in a pre-IND meeting whenever a master trial protocol is planned. As is common in recent guidance, the document ends with some clear examples of both basket and umbrella designs in a visual format. I heard there was significant interest in master trial protocols at the meeting, and I expect to see more oncology development programs making use of this tool in the next few years.

Text Copyright © 2019 Katrina Rogers