NCT04315155

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

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• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University of Utah · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Metastatic Adenocarcinoma

Interventions

Type	Name	Description
DRUG	Belinostat	Doublet Regimen Dose levels for Part 1: Belinostat Dose Level 1 (starting dose) 500 mg/m2 Dose Level 2 750 mg/m2 Dose Level 3 1000 mg/m2
DRUG	nivolumab	Doublet Regimen Dose levels for Part 1 Nivolumab Dose Level 1 (starting dose) 360 mg Dose Level 2 360 mg Dose Level 3 360 mg
DRUG	ipilimumab	Triplet and Doublet Regimen Dose Levels for Phase 2 Ipilimumab Doublet Dose n/a Triplet Dose 1 mg/kg
DRUG	nivolumab	Triplet and Doublet Regimen Dose Levels for Phase 2 Nivolumab Doublet Dose 360 mg IV Triplet Dose 3 mg/kg
DRUG	Belinostat	Triplet and Doublet Regimen Dose Levels for Phase 2 Belinostat Doublet Dose RP2D Triplet Dose RP2D

Timeline

• Start date: 2020-10-01
• Primary completion: 2023-09-01
• Completion: 2025-09-01
• First posted: 2020-03-19
• Last updated: 2020-10-28

Regulatory

• FDA-regulated drug study