Statistical Strength in Numbers: International Clinical Trials for Rare Cancers
Altogether, rare cancers account for about one-third of all cancer cases. Researchers believe this proportion will likely grow as molecular characterization reveals that even common cancers have rare subtypes, strengthening the public health rationale for finding safe and effective therapies for these tumors. For some rare cancers, however, the only practical way to carry out a meaningful clinical trial is for investigators around the world to work together, because no single country has access to a sufficient number of patients with a given tumor type.
—Dr. Jack Welch
“International trials for rare cancers offer many advantages over separate trials done in different countries or regions,” explained Dr. Jack Welch of the Clinical Investigations Branch in NCI’s Cancer Therapy Evaluation Program (CTEP). “By bringing patients together, international trials can accrue faster, and they offer lower collective administrative costs, shared infrastructure, centralized resources, and use of existing networks.”
On December 10, NCI and the American Society of Clinical Oncology (ASCO) convened a meeting of international stakeholders to explore ways to collaborate across borders on clinical trials for rare cancers. Nearly 100 representatives from 75 institutions participated in the day-long meeting, which was supported by CTEP, NIH’s Office of Rare Diseases Research (ORDR), NCI’s Office of Advocacy Relations (OAR), and ASCO. In addition to representatives from NIH, the FDA, the HHS Office for Human Research Protections, and NCI’s Clinical Trials Cooperative Group Program, attendees included investigators from Canada, France, Italy, Japan, Korea, the United Kingdom, the European Organisation for Research and Treatment of Cancer, and representatives of patient advocacy organizations and the pharmaceutical industry.
Building on previous meetings that examined international collaboration in clinical trials and how to design trials for rare cancers, this meeting focused on circumstances that make it impractical to perform a phase II or phase III trial solely in North America. Participants heard presentations on research on rare cancers in the international setting, leveraging patient advocacy for rare cancer trials, human subject and data privacy considerations, and other regulatory and administrative barriers. They also attended breakout sessions that explored five previously identified priority research areas: rare pediatric cancers, adult brain cancers, sarcoma, cholangiocarcinoma, and rare gynecologic malignancies.
“The potential rewards of international trials are great, in terms of generating results that will help doctors and patients make informed decisions about treatment options for rare cancers,” said Dr. Welch. “But, there are significant challenges to overcome.” Among the barriers discussed by meeting participants were varying regulatory requirements, duplicative layers of study review, intellectual property concerns of pharmaceutical companies, restrictive agreements between academic investigators and pharmaceutical concerns, lack of recognition for team science, and the need to harmonize administrative operations between clinical trial organizations performing these studies.
“Many of these challenges, however, can be overcome with early planning, frequent communication, and flexibility,” stressed Dr. Ted Trimble, also of CTEP’s Clinical Investigations Branch.
When it comes to conducting small-population trials, there are some important gaps that need to be addressed, explained Dr. Samir Khleif, head of the Cancer Vaccine Section in NCI’s Center for Cancer Research. “We need to explore new statistical models that might allow a higher error rate in one area, in order to accomplish the study with fewer patients,” he said.
At the meeting, participants learned how patient advocacy groups can help recruit participants for trials and serve as conduits of information between researchers and patient communities. Some charities and foundations sponsor research activities, and some even support research infrastructure.
International collaboration is as much art as it is science, explained NCI’s Dr. Jorge Gomez in a recent editorial on health diplomacy in the NCI Cancer Bulletin. Dr. Gomez pointed out that successful collaborations must also strengthen relationships among countries, increase research capacity for all collaborators, and serve as a model for others to follow. Although working across international borders poses some challenges, he noted, planning, communication, and collaboration is the key to overcoming those challenges.
“This meeting brought together a catalytic group spanning various domains that can continue to plan and communicate with the goal of getting new trials under way in the next 3 to 5 years,” said Dr. Welch. “A series of teleconferences and face-to-face meetings will be convened to explore available resources and prioritize next steps.”
—Karen Eddleman and Shannon P. Hatch