A Phase I Study Of Pazopanib With Either Erlotinib Or Pemetrexed In Patients With Advanced Solid Tumors

Summary

This is an open-label, two-arm, Phase I, dose escalation study to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) of pazopanib in combination with erlotinib (Arm A) or pazopanib in combination with pemetrexed (Arm B) in patients with advanced solid tumors. Patients will be enrolled in cohorts of 3 (in each arm) to receive escalating doses of pazopanib and erlotinib or pazopanib and pemetrexed. Dose escalation schemas for each study arm are described in the protocol. For each arm, the MTD regimen will be defined as the highest dose combination of the agents where no more than one out of six patients experiences a dose-limiting toxicity. Six to twelve additional patients in each arm will be studied with the MTD regimen to evaluate toxicity and pharmacokinetics. In arm A (erlotinib), a run-in phase with each drug separately will allow an evaluation of pharmacokinetics with each drug separately and also for the two drugs in combination. This will allow an assessment of potential drug-drug interactions. Pharmacokinetic endpoints will be AUC, Cmax, tmax and t1/2 of pazopanib, erlotinib, and pemetrexed, as well as pemetrexed clearance before and after administration of pazopanib in the extension cohort of Arm B. Antitumor activity will be assessed using RECIST criteria.

Timeline

Start

2007-11-15

Primary completion

2009-09-04

Completion

2009-09-04

Publications

• Background Dy GK, Infante JR, Eckhardt SG, Novello S, Ma WW, Jones SF, Huff A, Wang Q, Suttle AB, Ottesen LH, Adjei AA, Burris HA 3rd. Phase Ib trial of the oral angiogenesis inhibitor pazopanib administered concurrently with erlotinib. Invest New Drugs. 2013 Aug;31(4):891-9. doi: 10.1007/s10637-012-9887-6. Epub 2012 Nov 8.

Drugs

Indications