A Phase I/II Study of Erlotinib in Combination With Quinacrine in Patients With Advanced Non-Small-Cell Lung Cancer
PRIMARY OBJECTIVES:
I. To assess the safety and tolerability of the combination of erlotinib (erlotinib
hydrochloride) and quinacrine (quinacrine dihydrochloride) in patients with advanced
non-small-cell lung cancer. (Phase I) II. To determine the recommended phase II doses of the
combination of erlotinib and quinacrine in patients with advanced non-small-cell lung
cancer. (Phase I) III. To determine the progression free survival (PFS) of erlotinib and
quinacrine combination or erlotinib alone in patients with advanced non-small-cell lung
cancer. (Phase II)
SECONDARY OBJECTIVES:
I. To describe the dose limiting toxicity of the erlotinib and quinacrine combination.
II. To determine the pharmacokinetic profile of the erlotinib and quinacrine combination.
III. To determine objective response rate (complete response [CR]+partial response [PR]) and
clinical benefit rate (CR+PR+ stable disease [SD]) of the erlotinib and quinacrine
combination and erlotinib alone.
IV. To estimate overall survival (OS).
TERTIARY OBJECTIVES:
I. To examine change in nuclear factor kappa-light-chain-enhancer of activated B cells
(NF-κB) related genes in the pre and post treatment biopsy samples as a pharmacodynamic
marker of treatment with quinacrine.
II. To correlate expression of NF-κB related proteins in the pre-treatment tissue with
clinical activity of quinacrine and erlotinib combination.
III. To measure circulating tumor cells and correlate with response and survival.
OUTLINE: This is a phase I, dose escalation study of quinacrine dihydrochloride followed by
a phase II study.
PHASE I: Patients receive erlotinib hydrochloride orally (PO)daily on days 1-28 and
quinacrine dihydrochloride PO thrice daily (TID) on days, 1-7 and PO daily from days 8-28.
PHASE II: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive erlotinib hydrochloride PO daily on days 1-28.
ARM II: Patients receive erlotinib hydrochloride PO and quinacrine dihydrochloride PO thrice
daily (TID) on days, 1-7 and PO daily from days 8-28.
In both arms, courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Interventional
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) of quinacrine dihydrochloride in combination of erlotinib hydrochloride determined by dose-limiting toxicities: Phase I
28 days
Yes
Neelesh Sharma, MD PhD
Principal Investigator
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
United States: Food and Drug Administration
CASE8512
NCT01839955
June 2013
Name | Location |
---|---|
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center | Cleveland, Ohio 44106-5065 |
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center | Cleveland, Ohio 44195 |