AD HOC Trial: Artificial Intelligence-Based Drug Dosing In Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

Official title:

AD HOC Trial: Artificial Intelligence-Based Drug Dosing In Hepatocellular Carcinoma

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT05669339
• Other study ID #: UF-GI-015
• Secondary ID: OCR43006
• Status: Suspended
• Phase: Phase 1
• Start date: June 2024
• Est. completion date: April 2026

Study information

• Verified date: May 2024
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 12
• Est. completion date: April 2026
• Est. primary completion date: April 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Adults = eighteen years of age

• Biopsy proven advanced-stage hepatocellular carcinoma (HCC), as confirmed by pathological analysis.

• Not eligible for, or had disease progression after, surgical or locoregional therapies.

• Subjects must not have more than one active malignancy at the time of enrollment (Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen [as determined by the treating physician and approved by the PI] may be included).

• Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less.

• Child-Pugh liver function class A or B7

• Life expectancy of 12 weeks or more

• At least one untreated target lesion that could be measured in one dimension, according to the Response Evaluation Criteria in Solid Tumors (mRECIST).

• Must have lab values consistent with the following:

1. Platelet count = 60,000

2. Hemoglobin, =8.0 g/dL

3. INR =2.5

4. Albumin =2.5 g/dL

5. Total bilirubin, =5 mg/dL

6. ALT & AST =5 times the upper limit of normal

7. Creatinine = 2 times the upper limit of normal

• Written informed consent obtained from the subject and the subject agrees to comply with all the study-related procedures.

• Subjects of childbearing potential (SOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 20 months after the last dose of study drug to minimize the risk of pregnancy.

• Subjects with partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 8 months following the last dose of study drug.

Exclusion Criteria:

• Subjects of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 20 months after the last dose of study drug.

• Subjects who are pregnant or breastfeeding.

• History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications or protocol noncompliance, in the opinion of the treating physician.

• Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.

• Inability to follow up with treatment center for up to 12 weeks after enrollment

• Anticipated major surgery during the time of planned study

• Homozygosity for UGT1A1*28 via genotyping

• History of liver transplant

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• Irinotecan
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.
• Sonidegib
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).
• Sorafenib
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).

Locations

Country	Name	City	State
United States	University of Florida	Gainesville	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Florida	Sun Pharmaceutical Industries Ltd

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximally tolerated dose	Determine the maximum tolerated dose of irinotecan, sonidegib, and sorafenib	32 days
Secondary	Objective response rate	Determine the objective response rate, as measured by mRECIST 1.1 criteria	32 days
Secondary	Change in the biomarker AFP	Measure the change in the blood level of the biomarker AFP	32 days
Secondary	Change in the biomarker AFP-L3	Measure the change in the blood level of the biomarker AFP-L3	32 days
Secondary	Change in the biomarker DGC	Measure the change in the blood level of the biomarker DGC	32 days
Secondary	Change in the biomarker TGF-B	Measure the change in the blood level of the biomarker TGF-B	32 days