CHICAGO -- An idea floated during a 2013 ASCO annual meeting session became a reality here today, as the society announced its first-ever entry into sponsoring a clinical trial, the latest expansion in the evolution of the 51-year-old oncology society.
The ) study will assess off-label use of targeted therapies for various cancers while creating greater access of those drugs to more patients, according to Richard L. Schilsky, MD, ASCO's chief medical officer, who told 鶹ý that he first mentioned the concept 2 years ago during an educational session that focused on the challenges of delivering precision medicine services in a community setting.
"I didn't just want to identify challenges but also to suggest some solutions, and the idea resonated at the time with the attendees," he said. "Then someone asked if it was something that could actually be implemented."
Schilsky is no stranger to clinical trials, having chaired the former clinical trials group -- now the Alliance for Clinical Trials in Oncology -- for 15 years when he was at the University of Chicago.
After further developing the concept, he published " which first appeared online first as a Perspective piece in Nature Reviews-Clinical Oncology.
His next step was presenting the idea to ASCO's Cancer Research Committee, which approved the project, and then came several months trying to generate interest from pharmaceutical companies to contribute drugs and some funding.
Five companies -- AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Genentech, and Pfizer -- signed on with a total of 13 drugs with 15 unique genomic variants, and ASCO, which will sponsor, organize, and operate the project, also recruited three community-based study sites, two technology companies, three oversight committees, physicians, and patients as part of this diverse partnership.
Knowledge Gap
Edward S. Kim, MD, outgoing chair of the society's Cancer Research Committee, told 鶹ý that the study will mean that off-label use will be more than a just a case report.
"We'll be able to provide access to these targeted drugs in an organized way, putting them into the hands of more patients, and collecting important data that we can learn from that would otherwise not be available."
Schilsky said that ASCO's involvement would be filling a gap by giving those patients who are not responding to conventional therapies and not eligible for certain clinical trials, greater access to targeted drugs that may be a match to their tumor genetic profile, while providing oncologists and pharmaceutical companies with data that would not otherwise be captured.
The effort to collect "real-world" data on clinical outcomes to learn how these drugs can best be used outside of those indications that were Food and Drug Administration-approved, was not competitive but complementary to the work of other clinical trial operations, he said.
Schilsky is the project's principal investigator, Kim, Kim, who is chair of solid tumor oncology and investigational therapeutics at Carolinas HealthCare System (CHS), will serve as a site principal investigator. CHS’s Levine Cancer Institute will be one of the trial sites, together with Michigan Cancer Research Consortium, and the Cancer Resource Consortium of West Michigan.
The prospective, nonrandomized clinical trial will collect information on anti-tumor activity and toxicity of commercially available targeted therapies. All therapies will be single agent only at this time.
Funding will be primarily from ASCO; the clinical sites will receive per case costs for enrollment; the drugs will be provided at no cost by the pharmaceutical companies; the technology companies -- Syapse and Illumina -- will support the management, analysis, and interpretation of the study data; and ASCO will collaborate and share data with the Netherlands Center Personalized Cancer Treatment, which has a clinical trial protocol similar to TAPUR.
An Institutional Review Board will review the study protocol and consent form within the next few months, and ASCO has created three oversight committees:
- A Steering Committee that will oversee operations, establish data sharing and publication policies; review adding or removing drugs from the study; and approve additional clinical study sites
- A Molecular Tumor Board that will review proposed drug-target matches and suggest therapies on or off the study
- A Data and Safety Monitoring Board that will regularly review study results ensuring that severe or unexpected adverse events are carefully monitored; determine expansion or ending of enrollment of study cohorts; and determine when and where to release data.
Trial candidates will be patients with advanced cancer lacking standard treatment options, and include solid tumors, multiple myeloma, or non-Hodgkin lymphoma with a genomic variant known to be a drug target or to predict sensitivity to a drug.
Patients who meet the defined trial criteria, will be offered an available drug within the TAPUR protocol that targets their tumor's particular genomic variation, and if a relevant drug is not found, physicians can consult the Molecular Tumor Board for other potential therapies on or off the study.
Patients will be monitored for standard toxicity and efficacy outcomes such as tumor response, progression-free and overall survival, as well as treatment duration and serious adverse events. All anti-cancer drugs will be free, and routine clinical costs should be covered through the patient's insurance.
Schilsky said that ASCO will continue developing additional educational sessions related to the complexities of practicing precision medicine for next year's meeting, and that eventually TAPUR will be integrated into ASCO's data analytics platform that also was announced at the annual meeting.
Jane Perlmutter, PhD, a cancer survivor and advocate involved in many cancer clinical trials and activities, will work with TAPUR to integrate the patient perspective by coordinating patient advocate recruitment and training.
During a telephone interview she said that she would be using a patient advocate model similar the one employed in , an innovative neoadjuvant breast cancer trial that also involved multiple drug companies.