Carcinoma, Hepatocellular
Conditions
Brief summary
This open-label study will demonstrate proof-of-mechanism of HIF1A inhibition by a decrease of HIF1A mRNA after intravenous (IV) infusion of RO7070179 in participants with hepatocellular carcinoma (HCC) who have failed at least one line of systemic therapy. This will be a single arm study and all participants will receive RO7070179, 13 milligram per kilogram per week (mg/kg/week), 2-hour IV infusion on Days 1 and 4 during Week 1 of Cycle 1, followed by once weekly in 6 week cycle. Treatment with RO7070179 will be continued until disease progression or unacceptable toxicity.
Interventions
DRUGRO7070179
RO7070179 (13 mg/kg/week) will be administered as 2-hour IV infusion.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female of \>=18 years of age with the Eastern Cooperative Oncology Group (ECOG) performance status 0-1, Child-Pugh score of 5-7, and Life expectancy of 3 months or greater. * Confirmed to have HCC as described by the American Association for the Study of Liver Disease (AASLD). * Participants who have failed at least one line of systemic therapy for advanced stage HCC or participants who are ineligible or unable to tolerate the standard of care treatment. * Have measurable or evaluable disease. * Participants with normal major organ functions as defined by hemoglobin (HgB) \>= 8.5 gram/decilitre (dL), absolute neutrophil count (ANC) \>= 1000/microliter (mcL), platelet \>= 60,000/micL, aspartate aminotransferase/alanine transaminase (AST/ALT) \<= 3 x Upper Limit of Normal (ULN), total Bilirubin \<= 2 x ULN, creatinine \<= 2 x ULN. * Willingness to undergo two tumor biopsies: before and after administration of RO7070179.
Exclusion criteria
* Concurrent serious medical illness that could potentially interfere with protocol compliance (such medical illness will not include hepatitis or cirrhosis, as the degree of liver impairment caused by these diseases are covered by other
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline to Week 6 in HIF1A mRNA Level in Tumor Tissue | Pre-dose (baseline) and Week 6 |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline to Week 6 in HIF2 Tumor Concentrations | Pre-dose (baseline) and Week 6 |
| Change From Baseline to Week 6 in Vascular Endothelial Growth Factor (VEGF) Tumor Concentrations | Pre-dose (baseline) and Week 6 |
| Change From Baseline to Week 6 in Erythropoietin (EPO) Tumor Concentrations | Pre-dose (baseline) and Week 6 |
| Change From Baseline to Week 6 in Prolyl 4 Hydroxylase Tumor Concentrations | Pre-dose (baseline) and Week 6 |
| Change From Baseline to Week 6 in CD34/von Willebrand factor (VWF) Tumor Concentrations | Pre-dose (baseline) and Week 6 |
| Change in Blood Alpha-fetoprotein (AFP) Concentrations from Baseline | Week 1 and Week 4 for Cycle 1 and at Week 1 for subsequent treatment cycles |
| Time to Progression (TTP) According to Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST) | Every 12 weeks upto 24 Months |
| Percentage of Participants With Complete Response (CR) and Partial Response (PR) According to RECIST and mRECIST | Every 12 weeks upto 24 Months |
| Change From Baseline to Week 6 in hypoxia-inducible factor 1a (HIF1A) Tumor Concentrations | Pre-dose (baseline) and Week 6 |
| Progression Free Survival (PFS) According to RECIST and mRECIST | Every 12 weeks upto 24 Months |
| Overall Survival (OS) According to RECIST and mRECIST | Every 12 weeks upto 24 Months |
| Percentage of Participants With Tumor Growth According to RECIST and mRECIST | Every 12 weeks upto 24 Months |
| Maximum Observed Plasma Concentration (Cmax) | pre- and post-dose at Week 1, Week 6 |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | pre- and post-dose at Week 1, Week 6 |
| Area under the Concentration-Time Curve From Zero to 168 Hours [AUC (0-168 hours)] | pre- and post-dose at Week 1, Week 6 |
| Plasma Decay Half-Life (t1/2) | pre- and post-dose at Week 1, Week 6 |
| Duration of Response (DOR) According to RECIST and mRECIST | Every 12 weeks upto 24 Months |
Countries
United States
Outcome results
None listed