| General information |
| Database: | DB00138 |
| Objective: | a phase 1/2 study of E7050 (golvantinib) in combination with sorafenib in patients (pts) with advanced hepatocellular carcinoma (hepatocellular carcinoma):phase 1 results.G plus sorafenib (S) had an additive cell killing effect in a HepG2 hepatocellular cell viability assay, thus warranting further evaluation of the combination in hepatocellular carcinoma |
| Authors: | Bert H. O'Neil, etal |
| Title: | a phase 1/2 study of E7050 (golvantinib) in combination with sorafenib in patients (pts) with advanced hepatocellular carcinoma (hepatocellular carcinoma):phase 1 results |
| Journal: | J Clin Oncol |
| Year: | 2013 Gastrointestinal Cancers Symposium |
| PMID: | J Clin Oncol 31, 2013 (suppl 4; abstr 294) |
| Trial Design |
| Clinical Trial Id: | NCT01271504. |
| Agent: | golvatinib
|
| Target: | cMet and Eph receptor
|
| Cancer Type: | liver cancer |
| Cancer Subtype: | advanced hepatocellular carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | E7050 (golvantinib) + sorafenib |
| Study Type: | an ongoing openlabelphase I/II study |
| Key Patients Feature: | pts have advanced hepatocellular carcinoma, ChildPugh (CP) A or B, up to 2 prior regimens, including S. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | Cohort 1: 7 Golvatinib 200 mg qd+ Sorafenib 400mg bid Cohort 2: 6 G 300 mg qd + S 400mg bid |
| Treatment Info: | A 3+3 dose escalation design was used to determine the maximum tolerated dose (MTD) with planned doses of G (200 mg, 300 mg, 400 mg) PO qd each in combination with S 400 mg bid in 28 day cycles.The dose limiting toxicity (DLT) evaluation period was the first 28 days. Treatment continued until disease progression or development of unmanageable toxicities. Response was assessed by RECIST 1.1. |
| Primary End Point: | MTD, safety, PR, SD and treatmentrelated Aes |
| Secondary End Point: | NA |
| Patients Number: | 13 |
| Trial Results |
| DLT_MTD: | MTD was declared as G 200 mg qd and S 400 mg bid. |
| Objective Response Rate: | NA |
| Disease Control Rate: | Confirmed partial responses (PRs) were observed in 2/12 (17%) pts and durable SD was observed in 4/13 (31%) pts based on investigator assessment. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Cohort 1: 71% Nausea (G3 14%);57% Hypoalbuminemia (G3 14%);43% Each alk phos increase, hypocalcemia (G3 14% each), hyperbilirubinemia (G3 14%), and diarrhea.Cohort 2:100% Diarrhea (G3 33%);67% Each nausea/vomiting(G3 17%), increased AST/ALT, abdominal pain (G3 17%); 50% each alk phos increase and fatigue. |
| Conclusions: | G in combination with S appeared to demonstrate manageable toxicity in advanced hepatocellular carcinoma pts. The PRs and durable SD observed in this pretreated pt population appear favourable and support continued evaluation inphase II. |