Patient Perspectives in Cross-Over Arms in Clinical Oncology Trials

The Cholangiocarcinoma Foundation (CCF) has released a new white paper, “Cross-over arms in oncology clinical trials: An important consideration for patients,” highlighting a revolutionary approach to designing cancer clinical trials. The paper emphasizes the importance of patient-centric trial designs and introduces the concept of "cross-over" options, opening new doors for patients with limited treatment options. It also encourages sponsors, investigators and regulators to advance patient-centric trial designs.

The paper is authored by Wendy Selig, Founder of WSCollaborative, Rachna Shroff, MD, MS, FASCO, 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. The study presents key insights from patients and clinicians on the significance of incorporating cross-over options within clinical trials.

Patients with cancer often view participation in clinical trials as their best chance for effective therapy options when conventional treatments are insufficient. Traditionally, randomized 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 randomized to the control arm the opportunity to switch to the investigational arm upon disease progression. Such an approach minimizes the risk to participants of receiving ineffective control treatment and increases the attractiveness of trial enrollment 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.

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 pivotal trial, known as the ClarIDHy study, included a 2:1 randomization 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 enrollment.

“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.”

Patient advocacy organizations, such as the Cholangiocarcinoma Foundation, have played a crucial role in facilitating discussions between trial sponsors, clinicians, regulators and patients. Their efforts have led to more patient-friendly trial designs that offer hope to patients and improve the success of clinical trials.

The release of this landmark paper is a call to action for sponsors and regulators to embrace patient-centric trial designs to accelerate the development of promising cancer therapies and enhance patient access to innovative treatments.

For more information on the paper and its authors, please visit here.