| General information |
| Database: | DB00154 |
| Objective: | Thisphase 1 study was performed to establish the safety, tolerability, recommendedphase 2 dose (RP2D), and preliminary clinical activity of ganetespib in previously treated patients with advanced hepatocellular carcinoma. |
| Authors: | Goyal L, et al |
| Title: | a phase I and pharmacokinetic study of ganetespib (STA9090) in advanced hepatocellular carcinoma. |
| Journal: | Invest New Drugs. |
| Year: | 2015 |
| PMID: | 25248753 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | ganetespib
|
| Target: | VEGFR, cMET, human epidermal growth factor receptor 2, IGFIR, EGFR, and other Hsp90 client proteins
|
| Cancer Type: | liver cancer |
| Cancer Subtype: | advanced hepatocellular carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase I study |
| Key Patients Feature: | Patients with advanced hepatocellular carcinoma, ChildPugh A cirrhosis, progression on or intolerance to sorafenib, and ECOG PS less than and equal to 1(median age, 57 years old; male 71 %; Asian 36 %; hepatocellular carcinoma etiology (HBV 36 %, HCV 43 %, Hemachromatosis 7 %, unknown 21 %); Child Pugh Class (A 93 %, B 7 %); median number of prior treatments 2; median baseline AFP 70.1 ng/mL) |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | standard 3x3 dose escalation study at doses of 100 mg/m(2), 150 mg/m(2), and 200 mg/m(2) IV given on days 1, 8, and 15 of each 28day cycle. Objective response by RECIST version 1.1 criteria was evaluated by CT/MRI every 8 weeks. |
| Primary End Point: | to establish the safety, tolerability, recommendedphase 2 dose (RP2D), and preliminary clinical activity |
| Secondary End Point: | NA |
| Patients Number: | 14 |
| Trial Results |
| DLT_MTD: | The RP2D was determined to be 200 mg/m(2). One doselimiting toxicity, grade 3 lipasemia, was observed at the 100 mg/m(2) dose. |
| Objective Response Rate: | No objective responses were seen; one patient (7 %) had stable disease at 16 weeks. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median time to progression was 1.8 months |
| Median OS A vs. C: | median overall survival was 7.2 months. |
| Adverse Event(agent arm): | The most commonly seen AEs were diarrhea (93 %), fatigue (71 %), AST elevation (64 %), and hyperglycemia (64 %). The most common Gr 3/4 AEs were hyperglycemia (21 %) and lipasemia (21 %). One (7 %) patient had a fatal AE, septic shock, within 30 days of receiving the study drug. |
| Conclusions: | Ganetespib had a manageable safety profile in patients with advanced hepatocellular carcinoma who had progressed on at least one line of systemic therapy. The pharmacokinetic profile showed that ganetespib exposure in patients with mild hepatic dysfunction is similar to that seen in patients with normal liver function. Ganetespib showed limited clinical benefit in patients with advanced hepatocellular carcinoma in thisphase I trial. |