| General information |
| Database: | DB00152 |
| Objective: | thisphase I study investigated the maximumtolerated dose (MTD), safety, activity, pharmacokinetics (PK), and biomarkers of the mammalian target of rapamycin inhibitor, temsirolimus, combined with sorafenib in hepatocellular carcinoma (hepatocellular carcinoma). |
| Authors: | Kelley RK, et al |
| Title: | Temsirolimus combined with sorafenib in hepatocellular carcinoma: a phase I dosefinding trial with pharmacokinetic and biomarker correlates. |
| Journal: | Ann Oncol. |
| Year: | 2013 |
| PMID: | 23519998 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | temsirolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | liver cancer |
| Cancer Subtype: | advanced hepatocellular carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | temsirolimus+sorafenib |
| Study Type: | a phase I dosefinding trial with pharmacokinetic and biomarker correlates |
| Key Patients Feature: | Patients with incurable hepatocellular carcinoma and Child Pugh score less than and equal to B7 |
| Biomarker: | Alphafetoprotein (AFP) |
| Biomark Analysis: | NA |
| Control Group Info: | NA |
| Treatment Info: | patients were treated with sorafenib plus temsirolimus by 3 + 3 design. The doselimiting toxicity (DLT) interval was 28 days. The response was assessed every two cycles. PK of temsirolimus was measured in a cohort at MTD. |
| Primary End Point: | the maximumtolerated dose (MTD), safety, activity, pharmacokinetics (PK) |
| Secondary End Point: | NA |
| Patients Number: | 25 |
| Trial Results |
| DLT_MTD: | The MTD was temsirolimus 10 mg weekly plus sorafenib 200 mg twice daily. Among 18 patients at MTD, DLT included grade 3 handfoot skin reaction (HFSR) and grade 3 thrombocytopenia. Grade 3 or 4 related adverse events at MTD included hypophosphatemia (33%), infection (22%), thrombocytopenia (17%), HFSR (11%), and fatigue (11%). |
| Objective Response Rate: | NA |
| Disease Control Rate: | Two patients (8%) had a confirmed partial response (PR); 15 (60%) had stable disease (SD). Alphafetoprotein (AFP) declined more than and equal to 50% in 60% assessable patients. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Grade 3 or 4 related adverse events at MTD included hypophosphatemia (33%), infection (22%), thrombocytopenia (17%), HFSR (11%), and fatigue (11%). |
| Conclusions: | The MTD of sorafenib plus temsirolimus in hepatocellular carcinoma was lotheyr than in other tumor types. hepatocellular carcinomaspecificphase I studies are necessary. The observed efficacy warrants further study. |