Abstract
BackgroundPersonalized and effective treatments for pancreatic ductal adenocarcinoma (PDAC) continue to remain elusive. Novel clinical trial designs that enable continual and rapid evaluation of novel therapeutics are needed. Here, we describe a platform clinical trial to address this unmet need.MethodsThis is a phase II study using a Bayesian platform design to evaluate multiple experimental arms against a control arm in patients with PDAC. We first separate patients into three clinical stage groups of localized PDAC (resectable, borderline resectable, and locally advanced disease), and further divide each stage group based on treatment history (treatment naïve or previously treated). The clinical stage and treatment history therefore define 6 different cohorts, and each cohort has one control arm but may have one or more experimental arms running simultaneously. Within each cohort, adaptive randomization rules are applied and patients will be randomized to either an experimental arm or the control arm accordingly. The experimental arm(s) of each cohort are only compared to the applicable cohort specific control arm. Experimental arms may be added independently to one or more cohorts during the study. Multiple correlative studies for tissue, blood, and imaging are also incorporated.DiscussionTo date, PDAC has been treated as a single disease, despite knowledge that there is substantial heterogeneity in disease presentation and biology. It is recognized that the current approach of single arm phase II trials and traditional phase III randomized studies are not well-suited for more personalized treatment strategies in PDAC. The PIONEER Panc platform clinical trial is designed to overcome these challenges and help advance our treatment strategies for this deadly disease.Trial registrationThis study is approved by the Institutional Review Board (IRB) of MD Anderson Cancer Center, IRB-approved protocol 2020-0075. The PIONEER trial is registered at the US National Institutes of Health (ClinicalTrials.gov) NCT04481204.
Highlights
Personalized and effective treatments for pancreatic ductal adenocarcinoma (PDAC) continue to remain elusive
We have previously demonstrated that measurements of baseline enhancement and the morphology of the PDAC tumors are associated with stromal, genetic, physical, and clinical characteristics of the disease [12, 13]
We previously showed that the development of a sharpened interface at the tumor/parenchymal border was associated with longer Progression-Free Survival (PFS) and Overall survival (OS), compared to blurring of the tumor/parenchymal interface [14]
Summary
Personalized and effective treatments for pancreatic ductal adenocarcinoma (PDAC) continue to remain elusive. The emergence and acceptance of neoadjuvant, pre-operative approaches to localized PDAC has created an opportunity to evaluate novel therapies in earlier stage disease, potentially helping advance therapeutic strategies for all stages of PDAC. Many patients who undergo upfront surgery develop distant metastasis at a high rate within 6 months. This fact underscores the need for better selection for surgical management and provides a sound rationale for pre-operative therapy. The PREOPANC study suggested an improvement in disease free survival for patients who underwent neoadjuvant therapy as compared to upfront surgery for resectable/borderline resectable disease [3]. This study highlighted the potential beneficial role of neoadjuvant therapy for patients with radiologically localized disease at presentation. We detail a multi-institutional phase II randomized-controlled Bayesian platform trial for investigations of new and emerging therapies called PIONEER-Panc
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