Strategic Initiatives for Veterans with Lung Cancer

VALOR Trial

The VA Cooperative Studies Program (CSP) #2005 VALOR study is a randomized phase 3 clinical trial that evaluates optimal treatment for participants with operable early-stage NSCLC.²⁰ The trial is sponsored by the CSP, which is responsible for and provides resources for the planning and conduct of large multicenter surgical and clinical trials in VHA.²¹ The CSP #2005 VALOR study plans to enroll veterans with stage I NSCLC who will be treated with a surgical lobectomy or SBRT according to random assignment. An alternative surgical approach with a segmentectomy is acceptable, although patients in poor health who are only qualify for a wedge resection will not be enrolled. The CSP will follow each participant for at least 5 years to evaluate which treatment, if either, results in a higher overall survival rate. Secondary outcome measures are quality of life, pulmonary function, health state utilities, patterns of failure, and causes of death.

Although the study design of the VALOR trial is relatively straightforward, recruitment of participants to similar randomized trials of surgery vs SBRT for operable stage I NSCLC outside the VA has historically been very difficult. Three earlier phase 3 trials in the Netherlands and US closed prematurely after collectively enrolling only 4% of planned participants. Although a pooled analysis of 2 of these trials demonstrated a statistically significant difference of 95% vs 79% survival in favor of SBRT at a median follow-up of 40 months, the analysis was underpowered because only 58 of the planned 1,380 participants were enrolled.^22,23

The CSP #2005 VALOR study team was keenly aware of these past challenges and addressed many of the obstacles to enrollment by optimizing eligibility criteria and follow-up requirements. Enrollment sites were carefully selected after confirming equipoise between the 2 treatments, and study coordinators at each enrollment site were empowered to provide a leading role with recruitment. Multiple communication channels were established for constant contact to disseminate new best practices for recruitment as they were identified. Furthermore, a veteran-centric educational recruitment video, approved by the VA Central Institutional Review Board, was designed to help study participants better understand the purpose of participating in a clinical trial (www.vacsp.research.va.gov/CSP_2005/CSP_2005.asp).

After the first year of recruitment, researchers identified individual clinician and patient preferences as the predominant difficulty with recruitment, which was not easy to address. The CSP #2005 VALOR study team opted to partner directly with the Qualitative Research Integrated within Trials (QuinteT) team in the United Kingdom to adopt its methods to successfully support randomized clinical trials with serious recruitment challenges.^24,25 By working directly with the QuinteT director, the CSP #2005 VALOR team made a major revision to the informed consent forms by shifting focus away from disclosing potential harms of research to an informative document that emphasized the purpose of the study. The work with QuinteT also led to the creation of balanced narratives for study teams to use and for potential participants to read. These provide a more consistent message that describes why the study is important and why clinicians are no longer certain that surgery is the optimal treatment for all patients with operable stage I NSCLC.

The VALOR clinical trial, opened in 2017, remains open at only 9 VAMCs. As of early 2020, it has enrolled more participants than all previous phase 3 trials combined. Once completed, the results from CSP #2005 VALOR study will help clinicians and veterans with operable stage I NSCLC better understand the tradeoffs of surgery vs SBRT as an initial treatment option. Plans are under way to expand the scope of the trial and include investigations of pretreatment radiomic signatures and genetic markers from biopsy tissue and blood samples, to better predict when surgery or SBRT might be the best treatment option for an individual patient.