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S. O'Gara

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    P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P1.01-087 - A Phase I Study of Chloroquine with Carboplatin and Gemcitabine in Advanced Solid Tumors and NSCLC (ID 1628)

      09:30 - 17:00  |  Author(s): S. O'Gara

      • Abstract

      Autophagy is the catabolic degradation of cellular constituents that can promote cancer cell survival by maintaining cellular energy levels during periods of stress, including exposure to radiation or chemotherapy. The antimalarial, chloroquine (CQ), has received attention as an inhibitor of autophagy. The lysosomotropic properties of CQ are probably responsible for many of its biological effects. Manipulation of autophagy is a potentially exciting area for the development of new cancer treatments. Recently, accumulating evidence suggest that CQ can effectively sensitize cancer cells to the cell-killing effects of ionizing radiation and chemotherapeutic agents, thus suggesting its use as a sensitizer for conventional therapies. Hypothesis: CQ may sensitize chemotherapy-resistant tumor cells by inhibiting autophagy and enhance tumor response and survival of patients with solid tumors. Patients with non small cell lung cancer (NSCLC) squamous cell carcinoma subtype will be enrolled and followed for possible improved outcome with the addition of choloroquine to platinum doublet especially agents as Bevacuzimab can not be added to their standard doublet therapy. Patients with other advanced solid tumors will be eligible as long as carboplatin and Gemcitabine are considered an acceptable therapeutic option.


      Dose Level Patients(N) CQ mg/dl D-7-D21 Carboplatin AUC D1 Gemcitabine mg/m2 D1 &D8
      1 3-6 50 5 1,000
      2 3-6 100 5 1,000
      3 3-6 150 5 1,000
      4 3-6 200 5 1,000
      Expansion cohort 10-12 MTD 5 1,000
      Primary Objectives: The aim of this phase I study is to determine the adverse events (AE) and maximum tolerated dose (MTD) associated with adding chloroquine (CQ) to carboplatin and gemcitabine (CG) in patients with previously treated advanced solid tumors. Secondary Objectives: To estimate overall response rate (ORR), progression-free survival (PFS), and overall survival (OS); to determine the pharmacokinetics of CQ in combination with CG, and its effect on tumor burden by measurement of circulating tumor cells (CTCs). Methods: A single institution phase I dose-escalation study. Patients with advanced solid malignancies with no available standard of care treatment options, and ECOG performance status 0-2 are eligible. Sequential cohorts of 3-6 patients will be treated with escalating daily doses of oral CQ in addition to carboplatin and gemcitabine (Table 1). The study is ongoing and patient accrual is in the first cohort.

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