AD HOC Trial: Artificial Intelligence-Based Drug Dosing In Hepatocellular Carcinoma
University of Florida
Summary
This study will test the hypothesis that a novel combination of three drugs (sorafenib, sonidegib, and irinotecan), in conjunction with individually optimized doses, can be safely administered and lead to improved clinical outcomes in patients with hepatocellular carcinoma compared to standard of care. The main objective of this study is to establish safe dose ranges for the coadministration of sorafenib, sonidegib, and irinotecan in patients with hepatocellular carcinoma. Furthermore, we will collect data to inform the application of an artificial intelligence/computational approach to individual dosing of combination chemotherapy. Individualization of dosing will be achieved by using Phenotypic Personalized Medicine (PPM) to maximize treatment efficacy in patients with hepatocellular carcinoma, while minimizing toxicity. Drug efficacy will be assessed by measuring plasma circulating tumor DNA (ctDNA). Toxicity will be assessed by quantitating organ injury and patient tolerability. Recommended dosing for future studies will be based on the totality of the data.
Eligibility
- Age range
- 18–99 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Adults ≥ eighteen years of age * Biopsy proven advanced-stage hepatocellular carcinoma (HCC), as confirmed by pathological analysis; or confirmation of HCC from a LI-RADS 5 imaging score. * Not eligible for, or had disease progression after, surgical or locoregional therapies when these treatments are intended as sole, definitive therapy aimed at curing the disease, rather than as part of a combination therapy approach * Subjects must not have more than one active malignancy at the time of enrollment (Subjects with a prior or concurrent malignancy whose natural history o…
Interventions
- DrugIrinotecan
All subjects will be given either 25 mg/m2 (dose level -1), 50 mg/m2 (dose level 0), or 75 mg/m2 (dose level +1) irinotecan intravenously every 7 days.
- DrugSonidegib
All subjects will take 200 mg sonidegib orally either every 96 hours (dose level -1), every 48 hours (dose level 0), or every 24 hours (dose level +1).
- DrugSorafenib
All subjects will take 200 mg sorafenib orally either every 48 hours (dose level -1), every 24 hours (dose level 0), or every 12 hours (dose level +1).
Location
- University of FloridaGainesville, Florida