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Design of a Lung Cancer Master Protocol

Design of a Lung Cancer Master Protocol

Developing a potential therapy from the initial discovery stage through clinical testing and regulatory review is a complicated, expensive, and often inefficient process that can take up to 15 years. The current system is unsustainable. Included among the many challenges of drug development are the difficulties in recruiting cancer patients to clinical trials, the extensive bureaucratic processes required to initiate any clinical trial, and lengthy regulatory review. Modernizing this process with innovative approaches and new clinical trial designs is of high importance.

On March 12, 2013, Friends of Cancer Research hosted a workshop on the Design of a Lung Cancer Master Protocol. At this workshop, a multi-stakeholder group of experts 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 as well as 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.

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 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, CROs, 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 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.