| General information |
| Database: | DB00121 |
| Objective: | They conducted a singlearmphase 2 study of cediranib, a panVEGFR tyrosine kinase inhibitor, in patients with advanced hepatocellular carcinoma (hepatocellular carcinoma). |
| Authors: | Zhu AX, et al |
| Title: | Efficacy, safety, pharmacokinetics, and biomarkers of cediranib monotherapy in advanced hepatocellular carcinoma: a phase II study. |
| Journal: | Clin Cancer Res. |
| Year: | 2013 |
| PMID: | 23362324 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cediranib
|
| Target: | Vascular endothelial growth factor receptor 2
|
| Cancer Type: | liver cancer |
| Cancer Subtype: | advanced hepatocellular carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase II study |
| Key Patients Feature: | Patients with histologically confirmed measurable advanced hepatocellular carcinoma and adequate hematologic, hepatic, and renal functions |
| Biomarker: | Plasma levels of VEGF and PlGF increased and sVEGFR1, sVEGFR2, and Ang2 decreased after cediranib treatment. PFS was inversely correlated with baseline levels of VEGF, sVEGFR2, and bFGF and with ontreatment levels of bFGF and IGF1, and directly associated with ontreatment levels of IFN¦Ã. OS was inversely correlated with baseline levels of sVEGFR1, Ang2, TNF¦Á, CAIX, and CD34(+)CD133(+)CD45(dim) circulating progenitor cells and ontreatment levels of sVEGFR2. |
| Biomark Analysis: | Plasma levels of VEGF and PlGF increased and sVEGFR1, sVEGFR2, and Ang2 decreased after cediranib treatment. PFS was inversely correlated with baseline levels of VEGF, sVEGFR2, and bFGF and with ontreatment levels of bFGF and IGF1, and directly associated with ontreatment levels of IFN¦Ã. OS was inversely correlated with baseline levels of sVEGFR1, Ang2, TNF¦Á, CAIX, and CD34(+)CD133(+)CD45(dim) circulating progenitor cells and ontreatment levels of sVEGFR2. |
| Control Group Info: | single arm |
| Treatment Info: | cediranib 30mg orally once daily (4 weeks/cycle). |
| Primary End Point: | PFS at 3 months. |
| Secondary End Point: | response rates, overall survival (OS), pharmacokinetics (PK), and biomarkers for cediranib. |
| Patients Number: | 17 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | an estimated 3month PFS rate of 77% (60%, 99%). Median PFS was 5.3 (3.5, 9.7) months, stable disease was seen in 5/17 patients (29%), |
| Median OS A vs. C: | median OS was 11.7 (7.513.6) months. |
| Adverse Event(agent arm): | Grade 3 toxicities included hypertension (29%), hyponatremia (29%), and hyperbilirubinemia (18%). Cediranib PK were comparable to those seen in cancer patients with normal hepatic function. |
| Conclusions: | Despite the limitations of primary endpoint selection, cediranib at 30mg daily showed a high incidence of toxicity and preliminary evidence of antitumor activity in advanced hepatocellular carcinoma. Hepatic dysfunction did not seem to affect the steadystate PK of cediranib. Exploratory studies suggested proangiogenic and inflammatory factors as potential biomarkers of antiVEGF therapy in hepatocellular carcinoma. |