A Phase I Study Of Pazopanib With Either Erlotinib Or Pemetrexed In Patients With Advanced Solid Tumors
Status:
Completed
Trial end date:
2009-09-04
Target enrollment:
Participant gender:
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.