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Master Protocol

Friends of Cancer Research Moves Revolutionary New Clinical Trial Design Forward
 
Update - Lung Cancer Master Protocol Activation Announcement - 11/11/2013
The Lung Cancer Master Protocol was officially announced at the 2013 Conference on Clinical Cancer Research hosted by Friends of Cancer Research and the Engelberg Center for Health Care Reform at the Brookings Institution. The first trial to use the new multi-drug, multi-arm protocol will evaluate five compounds intended to treat squamous cell lung cancer. Genomic screening which will be used to assign enrolled patients to the treatment arms most likely to provide benefit. More information about the Lung Cancer Master Protocol will be available soon. 
 
Slides from the November 7, 2013 Lung Cancer Master Protocol Activation Announcement are available HERE.
 

The following five drugs, selected by an academic review panel, will be included in the initial trial: 

  • MEDI4736, from MedImmune, an anti-PD-L1 monoclonal antibody
  • AZD4547, from AstraZeneca, a FGFR tyrosine kinase inhibitor
  • Rilotumumab, from Amgen, a hepatocyte growth factor receptor c-MET inhibitor
  • Pictilisib, from Genentech/Roche, a PI3 kinase inhibitor, and
  • Palbociclib, from Pfizer, a CDK4/6 kinase inhibitor
 
The Issue: 

Taking a new drug from the initial discovery stage through clinical testing and regulatory review is complicated, expensive, and often inefficient. Trials are difficult to initiate, subject to lengthy regulatory review, infrastructure-intensive, and reliant on the enrollment of volunteers—all obstacles compounded by the fact that trials for new drugs are almost always conducted separately, even when multiple drugs are being developed to treat the same condition. And while the rise of personalized medicine has improved many aspects of patient care, it has also exacerbated the challenges of running a clinical trial. Small, targeted patient populations have made it more difficult to recruit qualified patients. Reliance on genetic testing increases infrastructure costs and complexity.

Our Work To Modernize the Clinical Trial Process: 
To continue our innovative work to address the issue of modernizing the process with innovative approaches and new clinical trial designs Friends of Cancer Research (Friends) hosted a workshop on the Design of a Lung Cancer Master Protocol on March 12, 2013. At this workshop, leaders from federal health and regulatory agencies, academic research centers, patient advocacy organizations and the private sector came together to reach consensus on the design of a biomarker-driven, multi-drug, multi-arm Phase 2/3 registration trial in lung cancer.
 
This trial, which was first proposed at the 2012 Conference on Clinical Cancer Research hosted by Friends of Cancer Research and the Engelberg Center for Health Care Reform at the Brookings Institution, has the potential to revolutionize and accelerate the way new biomarker-defined therapies are tested for lung cancer.
 
The trial also aims to serve as a model that can be used for other diseases. It also represents a new opportunity for patients in a setting where few clinical trials may be available or accessible, especially for those patients with very rare mutations.
 
During this recent day-long working group meeting, participants came to agreement on the overall trial design (including endpoints, patient population, biomarker screening, controls, and statistical analysis). This trial will utilize a broad, multi-marker screening platform. The ability to screen for a large number of alterations from the same sample is a key feature of this trial. This feature maximizes the information potential of patient tissue and maximizes the likelihood that any particular patient will be successfully matched to a biomarker-defined arm. This also reduces the burden on drug companies of having to find a diagnostic partner to continue the development of a biomarker-defined therapy. Another key feature is that all cooperative groups would be involved to enable rapid patient accrual. The master protocol could be amended for individual study arms depending on the features of a specific investigational agent at IRBs around the country rather than having new trials starting- this would greatly increase efficiency. The trial would be designed with the ultimate goal of FDA approval for those drugs that meet pre-specified efficacy criteria.
 
The workshop also led to consensus on the roles of different groups in the conduct of the trial. After approval by the NCI Thoracic Malignancy Steering Committee, the master investigational new drug (IND)  would be held by the Foundation for the National Institutes of Health (FNIH), who would hold contracts with all of the entities including trial sites, labs, contract research organizations, and companies. The trial would utilize a drug selection committee consisting of independent experts to determine what biomarkers and drugs would be studied in the trial. A Global Trial Oversight committee, consisting of members of FDA, NIH, FNIH, patient foundations and industry would also evaluate site management and data collection. The NCI SWOG cooperative group (one of the five cooperative groups that together comprise the NCI's National Clinical Trials Network) would be responsible for operational monitoring, quality control, tissue and data flow.
 
The immediate next steps for this project include writing the protocol, working with companies to select drug candidates, developing the governance structure, developing a template of data set expectations, and determining the overall cost estimate and staffing needs. It is anticipated that the protocol can be written within the next 2-3 months and that the governance structure can be developed based on I-SPY2 trial within the same timeframe. Friends of Cancer Research, along with our expert working group, are optimistically aiming to begin enrolling patients in early 2014.
 
Master Protocol Trial Design in the News