Early Phase Cancer Clinical Trial Design for Dose Finding of Treatment Combinations Across Patient Groups

• Activity Number: 62 - Topics in Adaptive Designs: Adaptive-Seamless, Group Sequential and Other Designs
• Type: Contributed
• Date/Time: Monday, August 3, 2020 : 10:00 AM to 2:00 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Bethany Horton*
• Companies: University of Virginia
• Keywords: Continual Reassessment Method; Dose-finding studies; Maximum tolerated dose combination; Clinical trials; Phase I designs; Ordered groups

Abstract

The proposed design allows for selection of the maximum tolerated dose combination (MTDC) for multiple groups. This work is motivated by an investigator initiated clinical trial designed to identify the MTDC among treatment combinations of erntinostat and capecitabine. The trial includes patients with high risk breast cancer who have undergone neoadjuvant chemotherapy and surgery, with and without radiation therapy. While it is unknown if patients receiving radiation therapy require a different treatment combination than those who have not received radiation therapy, it is reasonable to assume that the MTDC among those receiving radiation should be no higher than that of patients not receiving radiation treatment. Simulations compare the proposed to independent trials for each group, ignoring the group order information. Simulations show that when ignoring information on order, 20% of simulated trials result in MTDC selection that is out of order between groups. In addition, the proposed design selects the MTD more often and assigns more patients to the MTDC. CRM for treatment combinations with ordered groups ensures appropriate MTDC order and improves accuracy of MTDC selection.