| General information |
| Database: | DB00127 |
| Objective: | The phosphoinositide 3kinase/Akt/mammalian target of rapamycin pathway plays a critical role in the pathogenesis of hepatocellular carcinoma (hepatocellular carcinoma). they performed a singlearm, phase 1/2 study of everolimus in patients with advanced hepatocellular carcinoma. |
| Authors: | Zhu AX, et al |
| Title: | Phase 1/2 study of everolimus in advanced hepatocellular carcinoma. |
| Journal: | Cancer. |
| Year: | 2011 |
| PMID: | 21538343 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | everolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | liver cancer |
| Cancer Subtype: | advanced hepatocellular carcinoma not amenable to surgical or regional therapies |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase I/II study |
| Key Patients Feature: | Patients with histologically confirmed measurable advanced hepatocellular carcinoma, 02 prior regimens, and adequate hematologic, hepatic, and renal functions |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | everolimus at 5 mg/day or 10 mg/day orally (6 weeks/cycle). |
| Primary End Point: | a safe dosage of everolimus (phase 1) and progression free survival (PFS) at 24 weeks (phase 2). |
| Secondary End Point: | NA |
| Patients Number: | 28 |
| Trial Results |
| DLT_MTD: | No doselimiting toxicities were observed at the 5 mg/day (n = 3) or 10 mg/day (n = 6) dosage level inphase 1. Twentyfive patients received everolimus at 10 mg/day. |
| Objective Response Rate: | One patient (4%) had partial response (95% confidence interval [CI], 0.9%19.6%). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3.8 months (95% CI, 2.14.6).The estimated PFS rate at 24 weeks was 28.6% (95% CI, 7.9%49.3%). |
| Median OS A vs. C: | 8.4 months (95% CI, 3.921.1) |
| Adverse Event(agent arm): | Grade 34 adverse events included lymphopenia (n = 3), aspartate transaminase (n = 3), hyponatremia (n = 2), and 1 patient each with anemia, alanine transaminase, hyperglycemia, proteinuria, rash, and hypoxia. |
| Conclusions: | Everolimus was well tolerated in patients with advanced hepatocellular carcinoma, and 10 mgday was defined as thephase 2 dosage. Although the study did not proceed to the second stage ofphase 2, preliminary antitumor activity was observed with everolimus in patients with advanced hepatocellular carcinoma, most of whom had prior systemic treatment |