Evaluating Safety & Efficacy Belinostat Combo w Nivo Alone & w Ipi in Patients w Treated Metastatic/Advanced Carcinomas w ARID1A Lof Mutation — BENEFIT  

Metastatic Adenocarcinoma Clinical Trial

Official title: Ph I Study to Evaluate the Safety and Efficacy of Belinostat in Combination With Nivolumab Alone and With Ipilimumab in Patients With Previously Treated Metastatic or Advanced Carcinomas Enriched for ARID1A Loss of Function (Lof) Mutation

Status Withdrawn

Clinical Trial Summary

This is an open-label Phase I trial designed to determine the phase 2 recommended dose (RP2D) of belinostat in combination with nivolumab with or without ipilimumab.

Clinical Trial Description

Overall, the trial will assess dosing and safety of two regimens in the study population:

• The double regimen: belinostat in combination with nivolumab;

• The triplet regimen: belinostat in combination with nivolumab and ipilimumab. The trial will consist of two parts: Part 1 will establish the RP2D of belinostat in combination with nivolumab (doublet regimen) and Part 2 will assess the safety of the RP2D of belinostat in combination with nivolumab (doublet regimen) and ipilimumab (triplet regimen). In Part 1, the recommended phase 2 dose of belinostat will be determined by using an single-patient accelerated titration design confirmed by a modified 3+3 design.

Once the RP2D of belinostat is confirmed in Part 1, Part 2 will open to the expansion of the doublet regimen and begin assessing the triplet regimen. The assessment of safety for the triplicate regimen will follow a Bayesian approach as described in the Statistical Analysis section and Appendix 2.

Due to the expected contrast in toxicity profiles between immediate toxicity from belinostat at various dose levels and immune mediated toxicity from the doublet and the triplet regimens, the definition of dose-limiting toxicities and the DLT evaluation periods will differ for each regimen (doublet vs. triplicate). Patients will be managed according to the regimen administered.

Statistical Hypotheses: Belinostat in combination with nivolumab alone and with ipilimumab is safe and effective in patients with previously treated metastatic or advanced carcinomas with or without ARID1A loss of function (lof) mutations. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Metastatic Adenocarcinoma

• NCT number: NCT04315155
• Study type: Interventional
• Source: University of Utah
• Status: Withdrawn
• Phase: Phase 1
• Start date: October 2020
• Completion date: September 2025