A new whitepaper has introduced the concept of ‘cross-over’ options in cancer clinical trials, as a way to make trials more patient-centric in design.
‘Cross-over arms in oncology clinical trials: An important consideration for patients’ was published by the Cholangiocarcinoma Foundation (CCF) with the aim of opening new doors for patients with limited treatment options. It also encourages sponsors, investigators and regulators to advance patient-centric trial designs.
Traditionally, randomised controlled clinical trials (RCTs) have been considered the gold standard and the cornerstone of oncology research to ensure reliable study results. However, in cases where there is no standard of care or the current options are ineffective, the need for more patient-centric trial designs becomes imperative.
The paper advocates for the inclusion of ‘cross-over’ options within trials, allowing patients who have been randomised to the control arm the opportunity to switch to the investigational arm upon disease progression.
Such an approach minimises the risk to participants of receiving ineffective control treatment and increases the attractiveness of trial enrolment for patients. The inclusion of cross-over options has been debated within the cancer research community due to its impact on statistical analysis and endpoint interpretation. The authors argue, however, that this approach can be successful when thoughtfully designed with input from patient advocates.
Engaging patients in cancer clinical trials
A pivotal case study discussed in the paper revolves around the clinical development and regulatory approval of Tibsovo (ivosidenib) for IDH1-mutated cholangiocarcinoma patients. The trial, known as the ClarIDHy study, included a 2:1 randomisation between the investigational agent and placebo control, allowing for cross-over from the control arm to the experimental arm upon progression. Patient input was instrumental in shaping the flexible design features, which resulted in accelerated patient enrolment.
“Clinical trials are increasingly seen by clinicians and patients as part of an active treatment plan rather than a last resort,” Stacie Lindsey, CCF Founder and CEO. “This is especially true in cancers like cholangiocarcinoma, for which treatment options are severely limited. Listening to patients and providing flexibility in study designs is vital to getting patients on the best treatment plan and engaging patients in clinical trials.”
The paper is authored by Wendy Selig, Founder of WSCollaborative, Rachna Shroff, Professor of Medicine and Chief of GI Medical Oncology at the University of Arizona Cancer Center, Stacie Lindsey, CCF Founder and CEO, and Melinda Bachini, CCF Director of Patient Services.
Edited by Diana Spencer, Senior Digital Content Editor, Drug Discovery World