Entry Detail
| General information | |
| Database: | DB00462 |
| Objective: | This study examined the feasibility of combining pazopanib (Votrient), an oral antiangiogenic agent, with paclitaxel and carboplatin. |
| Authors: | Burris HA 3rd, et al |
| Title: | Phase I study of pazopanib in combination with paclitaxel and carboplatin given every 21 days in patients with advanced solid tumors. |
| Journal: | Mol Cancer Ther |
| Year: | 2012 |
| PMID: | 22679111 |
| Trial Design | |
| Clinical Trial Id: | NCT00388076 |
| Agent: | pazopanib |
| Target: | Plateletderived growth factor receptor Mast/stem cell growth factor receptor Vascular endothelial growth factor receptor 2 |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | pazopanib + paclitaxel and carboplatin |
| Study Type: | a phase I, multicenter, openlabel, dosefinding study |
| Key Patients Feature: | Eligible patients had a confirmed histologic or cytologicdiagnosis of cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, adequatebone marrow, renal, and hepatic function as well asperipheral neuropathy of grade 1 or less |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | This 3 + 3 doseescalationphase I study evaluated the maximumtolerated regimen (MTR) of daily pazopanib in combination with paclitaxel 175 mg/m(2) and carboplatin [dosed at area under the curve (AUC) 5 or 6] given every 21 days in patients with advanced solid tumors. Plasma samples were collected to evaluate the effect of pazopanib on the pharmacokinetics of paclitaxel and carboplatin. |
| Primary End Point: | DLT |
| Secondary End Point: | the pharmacokinetics[clearance and maximal concentration (Cmax) for paclitaxel |
| Patients Number: | 34 |
| Trial Results | |
| DLT_MTD: | The most common doselimiting toxicities were neutropenia and thrombocytopenia. |
| Objective Response Rate: | In this phase I trial, there were 2 complete responses and 4 partial responses. Objective responses were observed at the MTR (paclitaxel 175 mg/m2, carboplatin AUC5, and pazopanib 200 mg) and included complete responses in 2 patients with esophageal cancer, one of whom had prior treatment with combination docetaxel and oxaliplatin, and one who was chemotherapy naive, and a partial response in a patient with smallcell lung cancer who had received one prior line of therapy. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common doselimiting toxicities were neutropenia and thrombocytopenia. |
| Conclusions: | Coadministration of pazopanib increased exposure to paclitaxel and carboplatin and likely contributed to this effect. Given the antitumor activity of this regimen, further studies are underway to determine a clinically tolerable schedule of pazopanib with paclitaxel and carboplatin. |