The goal of the study is to find the best dose of pacritinib when given in combination with erlotinib.
Name: Pacritinib
Type: DrugPhase I (pacritinib and erlotinib) Phase II (pacritinib and erlotinib)
Name: Erlotinib
Type: DrugPhase I (pacritinib and erlotinib) Phase II (pacritinib and erlotinib)
Description: The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. Dose escalations will proceed until the MTD has been reached. A patient is evaluable for DLT assessment only during Cycle 1 of treatment. If the patient is not able to be treated on Day 1 of Cycle 2, then s/he is still considered in Cycle 1 active treatment and can experience a DLT. Once the patient has been treated in Cycle 2, s/he will no longer be evaluated for DLTs in all subsequent cycles.
Measure: Dose-limiting toxicities and maximum tolerated dose (MTD) - Phase I only Time: Completion of cycle 1 of all Phase I patients (estimated to be 1 year)Description: Partial response + complete response per RECIST 1.1 criteria Study terminated prior to enrolling any phase II participants Complete response (CR) = disappearance of all target lesions, non-target lesions, and normalization of tumor marker level Partial response (PR) = at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline of sum diameters
Measure: Response rate - Phase II only Time: Up to 5 yearsDescription: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
Measure: Adverse events (toxicities) Time: 30 days post completion of treatment (estimated to be 9 months)Description: Percentage of patients who achieve complete response, partial response, or stable disease per RECIST 1.1 criteria. Complete response (CR) = disappearance of all target lesions, non-target lesions, and normalization of tumor marker level Partial response (PR) = at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline of sum diameters Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measure: Disease control rate (DCR) Time: Up to 5 yearsDescription: PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progressive disease (PD) = at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, appearance of one or more non-target lesion(s) and/or unequivocal progression of existing non-target lesions
Measure: Progression-free survival (PFS) Time: Up to 5 yearsDescription: Overall survival is defined as the time interval from date of diagnosis to date of death from any cause.
Measure: Overall survival (OS) Time: Up to 5 yearsAllocation: Non-Randomized
Parallel Assignment
There is one SNP
Patients with mutations in T790M are eligible if they have progressed after treatment with a third generation EGFR tyrosine kinase inhibitor (osimertinib), but otherwise patients must have EGFR T790M negative or unknown status. --- T790M ---
Patients with mutations in T790M are eligible if they have progressed after treatment with a third generation EGFR tyrosine kinase inhibitor (osimertinib), but otherwise patients must have EGFR T790M negative or unknown status. --- T790M --- --- T790M ---