Personalizing Precision Oncology Clinical Trials in Latin America: An Expert Panel on Challenges and Opportunities

In this precision oncology era, where molecular profiling at the individual patient level becomes increasingly accessible and affordable, more and more clinical trials are now driven by biomarkers, with an overarching objective to optimize and personalize disease management. As compared with the conventional clinical development paradigms, where the key is to evaluate treatment effects in histology-defined populations, the choices of biomarker-driven clinical trial designs and analysis plans require additional considerations that are heavily dependent on the nature of biomarkers (eg, prognostic or predictive, integral or integrated) and the credential of biomarkers’ performance and clinical utility. Most recently, another major paradigm change in biomarker-driven trials is to conduct multi-agent and/or multihistology master protocols or platform trials. These trials, although they may enjoy substantial infrastructure and logistical advantages, also face unique operational and conduct challenges. Here we provide a concise overview of design options for both the setting of single-biomarker/single-disease and the setting of multiple-biomarker/multiple-disease types. We focus on explaining the trial design and practical considerations and rationale of when to use which designs, as well as how to incorporate various adaptive design components to provide additional flexibility, enhance logistical efficiency, and optimize resource allocation. Lessons learned from real trials are also presented for illustration.

Download Full-text

OCTANE: Oncology Clinical Trial Annotation Engine

JCO Clinical Cancer Informatics ◽

10.1200/cci.18.00145 ◽

2019 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Jia Zeng ◽

Md Abu Shufean ◽

Yekaterina Khotskaya ◽

Dong Yang ◽

Michael Kahle ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

False Positive Rate ◽

False Negative ◽

False Negative Rate ◽

Cancer Center ◽

Precision Oncology ◽

Expert Review ◽

Oncology Clinical Trial ◽

Oncology Clinical Trials

PURPOSE Many targeted therapies are currently available only via clinical trials. Therefore, routine precision oncology using biomarker-based assignment to drug depends on matching patients to clinical trials. A comprehensive and up-to-date trial database is necessary for optimal patient-trial matching. METHODS We describe processes for establishing and maintaining a clinical trial database, focusing on genomically informed trials. Furthermore, we present OCTANE (Oncology Clinical Trial Annotation Engine), an informatics framework supporting these processes in a scalable fashion. To illustrate how the framework can be applied at an institution, we describe how we implemented an instance of OCTANE at a large cancer center. OCTANE consists of three modules. The data aggregation module automates retrieval, aggregation, and update of trial information. The annotation module establishes the database schema, implements data integration necessary for automation, and provides an annotation interface. The update module monitors trial change logs, identifies critical change events, and alerts the annotators when manual intervention may be needed. RESULTS Using OCTANE, we annotated 5,439 oncology clinical trials (4,438 genomically informed trials) that collectively were associated with 1,453 drugs, 779 genes, and 252 cancer types. To date, we have used the database to screen 4,220 patients for trial eligibility. We compared the update module with expert review, and the module achieved 98.5% accuracy, 0% false-negative rate, and 2.3% false-positive rate. CONCLUSION OCTANE is a general informatics framework that can be helpful for establishing and maintaining a comprehensive database necessary for automating patient-trial matching, which facilitates the successful delivery of personalized cancer care on a routine basis. Several OCTANE components are publically available and may be useful to other precision oncology programs.

Download Full-text