UC Davis Comprehensive Cancer Center patients will soon be part of an unprecedented clinical trial designed to improve access to promising therapies and speed development of effective treatments for an advanced form of lung cancer, the leading cancer killer of both men and women.
The approach, known as Lung-MAP (Lung Cancer Master Protocol), or S1400, is the product of a unique public-private collaboration among the National Cancer Institute (NCI), SWOG Cancer Research, Friends of Cancer Research, the Foundation for the National Institutes of Health (FNIH) and five pharmaceutical companies. It is the first of several planned large, genomically-driven trials that will be conducted by the NCI’s newly formed National Clinical Trials Network.
Lung-MAP’s strategy uses cutting-edge genomic profiling to match patients with late-stage squamous cell carcinoma to investigational treatments that target the molecular drivers of their individual tumors.
David Gandara, an internationally renowned oncologist and lung cancer expert and director of the UC Davis Thoracic Oncology Program, is a lead architect of the effort and serves as one of three leaders of the national trial.
“This is an entirely new way of looking at the development of cancer drugs,” said Gandara. “This is no longer business as usual. This approach changes the paradigm.”
Frustrated with the slow pace of lung cancer clinical trials of experimental therapies and their high failure rate, he talked to NCI officials more than 10 years ago about a more innovative approach.
“If you think about both the monetary investment and also the patient resources, hundreds of millions of dollars and clinical trials enrolling many tens of thousands of patients are wasted because we have an ineffective way of developing new anti-cancer drugs,” he said.
Video: Dr. David Gandara on the unprecedented approach to lung
cancer clinical trials.
Lung-MAP aims to establish a model of clinical testing that more efficiently meets the needs of patients, clinical investigators and drug developers. Instead of having to undergo multiple diagnostic tests to determine eligibility for many different studies, enrollees are tested just once according to a “master protocol” and assigned to one of five different trial arms, each simultaneously testing a different drug from a different developer. The approach is cost-effective for researchers because it gives them easier access to relevant enrollees based on their genomic profiles, and ensures patients better access to promising drugs.
Lung cancer is notoriously complex and heterogeneous; different tumors have vastly different biological properties and responses to treatment. Although the development of therapies targeted to these genetic differences has improved many aspects of patient care, it has also made running clinical trials more challenging since recruiting enough eligible patients any single trial is difficult.
Gandara said the investigators chose squamous cell carcinoma for the experimental master protocol because it has not enjoyed the advances seen in the more common type of non-small cell lung cancer, adenocarcinoma.
The trial will initially test five experimental drugs – four targeted therapies and an immunotherapy. Researchers anticipate that each year approximately 1,200 patients will be screened for more than 200 cancer-related genes for genomic alterations.
Lung-MAP is also more flexible than traditional clinical trial models. Whereas typical clinical trials require the development of new protocols (documents that detail precisely how a trial is to be conducted) for each new drug tested, Lung-Map uses a single master protocol, which can be amended as needed as drugs enter and exit the trial. As designed, the protocol will not disrupt established infrastructure or patient outreach efforts.
“Traditional clinical trials have long imposed significant recruitment and infrastructure burdens on researchers and patients, with frustratingly slow results,” said Marie Freire, president and executive director of the FNIH. “This master protocol will allow multiple enrollees to be tested once and assigned to a treatment rather than separate tests for separate trials with most patients ineligible.”
Lung-MAP will be conducted at more than 500 medical centers, including UC Davis Comprehensive Cancer Center. It will include all of the NCI’s cooperative groups, led by SWOG, as part of the NCI’s National Clinical Trials Network. UC Davis begins recruiting patients today.
If successful in hastening the accrual of patients to trials and the development of effective new drugs for squamous cell lung cancer, Gandara said the collaborators will branch out with the same approach to clinical trials for other types of cancer.
In addition to Gandara, other Lung-MAP leaders at UC Davis are Primo “Lucky” Lara, a medical oncologist who will serve as co-principal investigator for one of the five drug trial arms, and Philip Mack, director of molecular pharmacology at the cancer center, who serves as co-chair for translational medicine on the trial.
UC Davis Comprehensive Cancer Center is the only National Cancer Institute-designated center serving the Central Valley and inland Northern California, a region of more than 6 million people. Its specialists provide compassionate, comprehensive care for more than 10,000 adults and children every year, and access to more than 150 clinical trials at any given time. Its innovative research program engages more than 280 scientists at UC Davis, Lawrence Livermore National Laboratory and Jackson Laboratory (JAX West), whose scientific partnerships advance discovery of new tools to diagnose and treat cancer. Through the Cancer Care Network, UC Davis collaborates with a number of hospitals and clinical centers throughout the Central Valley and Northern California regions to offer the latest cancer care. Its community-based outreach and education programs address disparities in cancer outcomes across diverse populations. For more information, visit cancer.ucdavis.edu.