CCSG Pilot: Pulse-dose Lapatinib Combined with Paclitaxel for the Treatment of Recurrent, Platinum-resistant Ovarian Cancer

Grants and Contracts Details


Abstract Currently, there is no standard regimen for platinum-resistant ovarian cancer. Clinicians regularly prescribe dose-dense weekly paclitaxel, but response rates are low, so novel treatment strategies are urgently needed. Inadequate response to paclitaxel is associated with drug resistance mediated by ABCB1. In our preliminary data, we demonstrate that the combination of paclitaxel and lapatinib is synergistic at clinically achievable concentrations and that synergy is mediated by inhibition of ABCB1. A phase 1 trial combining nab-paclitaxel (Abraxane) and pulse-dose lapatinib showed clinical benefit in the majority of patients treated, was well tolerated, and achieved plasma concentrations associated with synergy in our preclinical models. Therefore, we propose a phase I dose-escalation study of paclitaxel and pulse-dose lapatinib in patients with platinum-resistant ovarian cancer. We hypothesize that the lapatinib pulse-dose schedule is pharmacologically optimized, achieving adequate plasma concentrations for paclitaxel synergy while balancing convenience and minimizing adverse effects. This proposal aims to determine the recommended phase II dose of paclitaxel and lapatinib for the treatment of recurrent, platinum-resistant ovarian cancer. We will conduct a phase I dose-escalation study of paclitaxel and lapatinib in patients with platinum-resistant ovarian cancer using the BION design. We will assess the plasma concentration of lapatinib and paclitaxel with a validated LC MSMS assay, and we will evaluate ABCB1 expression in cell-free RNA with NanoString. We will also assess patient-reported adverse effects with validated instruments. This application is both scientifically and clinically innovative. We are the first to evaluate lapatinib as an ABCB1 inhibitor in a clinical trial and the first to combine lapatinib and paclitaxel for ovarian cancer. We employ a novel, pulse-dosing method that achieves required plasma concentrations for synergy but requires only two days of oral dosing per week.
Effective start/end date7/1/206/30/23


  • National Cancer Institute


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