| General information |
| Database: | DB00129 |
| Objective: | Thisphase I study was designed to determine the maximum tolerated dose (MTD) of everolimus given with sorafenib 400mg twice daily in patients with advanced hepatocellular carcinoma of ChildPugh class A liver function who were naive to systemic therapy. |
| Authors: | Finn RS, et al |
| Title: | Phase I study investigating everolimus combined with sorafenib in patients with advanced hepatocellular carcinoma. |
| Journal: | J Hepatol |
| Year: | 2013 |
| PMID: | 23928403 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | everolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | liver cancer |
| Cancer Subtype: | advanced hepatocellular carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | everolimus+ sorafenib |
| Study Type: | a phase I study |
| Key Patients Feature: | patients with advanced hepatocellular carcinoma of ChildPugh class A liver function who were naive to systemic therapy. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Everolimus given with sorafenib 400mg twice daily was initiated at 2.5 mg once daily and increased per a Bayesian sequential doseescalation scheme based on the doselimiting toxicities experienced within the first 28 days of treatment |
| Primary End Point: | Adverse events were assessed continuously. Efficacy was evaluated using the best overall response rate per RECIST. |
| Secondary End Point: | NA |
| Patients Number: | 30 |
| Trial Results |
| DLT_MTD: | 25 were evaluable for MTD determination. One out of 12 patients treated with everolimus 2.5mg once daily and 6 out of 13 patients treated with everolimus 5.0mg once daily experienced a doselimiting toxicity, most commonly thrombocytopenia (n=5). |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 4.5 months, 2.5mg cohort 1.8 months, 5.0mg cohort |
| Median OS A vs. C: | 7.4 months, 2.5mg cohort 11.7 months, 5.0mg cohort |
| Adverse Event(agent arm): | All patients experienced 1 adverse event, most commonly diarrhea (66.7%), handfoot skin reaction (66.7%), and thrombocytopenia (50.0%). Best overall response was stable disease (62.5% and 42.9% in the 2.5mg and 5.0mg cohorts, respectively). |
| Conclusions: | In patients with advanced hepatocellular carcinoma, the everolimus MTD in combination with standarddose sorafenib was 2.5mg once daily. The inability to achieve a biologically effective everolimus concentration at the MTD precludedphase II study of this combination. |