FDA Center for Drug Evaluation & Research Director Janet Woodcock, MD, gave some advice to drug developers looking to shorten the clinical development time for new treatments, particularly in oncology: it will be participation in innovative combination trials that will really cut development time – not simply conducting smaller, shorter studies of single agents.

Woodcock used the platform of an April 12 Friends of Cancer Research forum on Breakthrough Therapies to continue to push for greater adoption of clinical trial master protocols that allow for the simultaneous study of multiple targeted oncology therapies from different drug sponsors as an alternative to traditional, single-agent registration studies.

FDA – in partnership with Friends of Cancer Research and others – set up the first, the Lung Master Cancer Protocol (Lung-MAP) in squamous cell lung cancer. Also see "Lung Cancer “Master Protocol” Eyed As Paradigm-Changing Approach To Drug Development" - Pink Sheet, 18 November, 2013. The master protocol concept was tested earlier in two smaller models: a breast-cancer study (I-SPY 2) and a lung cancer trial (BATTLE). Also see "Biomarkers Consortium Launches Adaptive Trial To Test Targeted Breast Cancer Drugs" - Pink Sheet, 19 March, 2010.

Other, larger, master protocols to build on the Lung-MAP model are under discussion – but the trial designs continue to linger on the drawing board as collaborators slowly make decisions about governance and protocol elements.

Woodcock has been an enthusiastic advocate for master protocols as a way to ensure that patients enrolled in clinical trial are more likely to get an effective treatment. At the Friends of Cancer Research briefing, she made a case that sponsors can also save time in the clinic – and reach approval sooner – by participating in collaborative studies.

“I don’t think squeezing any more time out of the FDA review, or squeezing any more time out of any one trial is necessary. I think we need to do trials differently,” Woodcock said.

Woodcock made her comments in response to a suggestion from Bristol-Myers Squibb Co. Senior VP-Global Regulatory, Safety & Biometrics Mathias Hukkelhoven, PhD, that industry needs FDA to be more flexible on requirements that every agent in a combination first must be individually approved before the agency will consider the combo. We need “creative solutions that minimize the risk but optimize the chances for detecting something sooner,” Hukkelhoven said.

“I agree with you that the paradigm has to change, but it’s not the FDA,” Woodcock countered. She pointed out that FDA published a final guidance document on co-developing multiple investigational agents for use in combination in 2013. That document was submitted to FDA by Friends of Cancer Research, and the agency adopted it largely as written. Also see "Co-Development Guidance Gives More Attention To IND, NDA/BLA Submissions" - Pink Sheet, 17 June, 2013.

Studying different investigational products in combination is certainly “doable,” Woodcock said, and FDA is fully on board. But Woodcock wants to take it a step further: “If we’re going to have standing trials, especially where you have small targeted patient subgroups in cancer, we are going to need trials were we can investigate multiple options in combination. We’ve got to rethink how we do drug development if we want to shorten this process.”

“What eats up those five to seven to 10 years in clinical development?” she asked. “It’s going from one protocol to another.”

The logistics of adding and revising protocols and trial centers are part of the reason for the long timelines for drug development, Woodcock said. “You do Phase I with one protocol, and then you have to start designing the Phase II and you do a protocol development, and then you get some [clinical] centers on board, and you get a CRO, and you make the agreements. It takes forever.”

Those are “unacceptable time frames” when you think of the patients who are waiting for new therapies, Woodcock said. “It’s preventable by doing things differently.”

Despite the clear advantages of master protocols, so far they have been relatively few and far between. They are complicated and difficult to set up; many sponsors as hesitant to cede control of promising new agents to a third party overseeing the trial; and there is a concern that such protocols would allow for direct, and perhaps unfavorable, comparisons between products.

Woodcock acknowledged those challenges. “It’s very hard for companies – they have a huge investment that they’ve made – to give up control and to cede that to another party,” she said. “But if we’re going to make progress…we are going to need standing protocols where we can…answer these questions in a timely manner.”

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