Clinical Trial: Phase 1/2 Study of ARQ 087 in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase 1/2 Study of ARQ 087 in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations, Including Intrahepatic Cholangiocarcinoma With FGFR2 Gene Fusion

Brief Summary: This is an open-label, Phase 1/2, dose escalation and signal finding study of ARQ 087 administered to subjects with advanced solid tumors with FGFR genetic alterations, including intrahepatic cholangiocarcinoma (iCCA) with FGFR2 gene fusion. The study is designed to explore the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ARQ 087 and to define a RP2D of ARQ 087.

Detailed Summary:
Sponsor: ArQule

Current Primary Outcome: Adverse events graded by CTCAE v4.03 as a measure of the safety and tolerability profile of ARQ 087 [ Time Frame: Assessed at each scheduled visit up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 24 weeks ]

Original Primary Outcome: Assess the safety and tolerability of ARQ 087 in subjects with advanced solid tumors by monitoring frequency and severity of adverse events [ Time Frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 24 weeks ]

Current Secondary Outcome:

  • Characterize the pharmacokinetic (PK) profile of ARQ 087 [ Time Frame: Part 1: t=Days 1, 2, 3, and 4. Cohort 5+: t=Days 1, 2, 8, 15, 22, and 23 of Cycle 1; and t=Days 1 and 15 of subsequent cycles ]
    Single dose PK parameters include the peak plasma concentration (Cmax), area under the plasma concentration vs. time curve (AUC), and half-life of ARQ 087
  • Assess pharmacodynamic (PD) activity of ARQ 087 [ Time Frame: Part 1 t=Days 1, 2, 3, and 4. For Cohort 5+: t=Days 1, 8, 15, 22 of Cycle 1; and t=Days 1 of Cycles 2-5. For Part 2: t=Day 1 of Cycle 1-6 ]
    PD parameters include changes of phosphate, glucose, and FGF 19, 21, and/or 23
  • Evaluate dose limiting toxicity (DLT) graded per CTCAE v4.03 to determine the recommended Phase 2 dosing (RP2D) regimen [ Time Frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 24 weeks ]
  • Evaluate further the RP2D of ARQ 087 in subjects with FGFR genetic alterations, including subjects with iCCA with FGFR2 gene fusion (Part 2; Expanded Cohort, signal finding) [ Time Frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 24 weeks ]
  • Evaluate tumor response assessed by RECIST v1.1 after treatment with ARQ 087 [ Time Frame: Baseline and every 8 weeks or as otherwise clinically indicated ]


Original Secondary Outcome:

  • Assess the pharmacokinetic profile (Area under the curve) of ARQ 087 [ Time Frame: During the first 28 days of treatment for each dose level ]
    Blood sampling to assess the pharmokinetic profile (Area under the curve) of ARQ 087.
  • Assess pharmacodynamic activity [ Time Frame: Up to treatment discontinuation ]
    Blood sampling to provide information on tumor FGFR protein expression using immunohistochemistry (IHC).
  • Determine preliminary evidence of activity as defined by standard imaging assessments [ Time Frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 24 weeks ]
  • Determine recommended Phase 2 dose [ Time Frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 24 weeks ]


Information By: ArQule

Dates:
Date Received: December 14, 2012
Date Started: December 2012
Date Completion: December 2017
Last Updated: December 22, 2016
Last Verified: December 2016