 Enrolled patients will remain on their assigned dose level until unacceptable toxicity or disease progression occurs. During dose escalation phase, if more than 34 of the evaluable patients at a dose level experience dose limiting toxicities DLT, this dose level will be considered having exceeded MTD. Once MTD is identified during dose escalation phase, the MTD dose level will be expanded in the expansion phase to enroll additional patients to ensure that at least 10 patients are evaluable for safety at the MTD. 