Clinical Trial: A Phase I Study of LXS196 in Patients With Metastatic Uveal Melanoma.

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase I, Multi-center, Open-label, Study of LXS196, an Oral Protein Kinase C Inhibitor, in Patients With Metastatic Uveal Melanoma

Brief Summary: This study is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of LXS196 as a single agent in patients with metastatic uveal melanoma.

Detailed Summary:
Sponsor: Novartis Pharmaceuticals

Current Primary Outcome:

  • Incidence of dose limiting toxicities (DLTs) (Dose escalation only) [ Time Frame: Cycle 1 in dose escalation ]
    cycle = 28 days
  • Incidence and severity of adverse events and serious adverse events, including changes in laboratory parameters, vital signs and ECGs graded as per NCI CTCAE version 4.03 (All patients) [ Time Frame: Continuously throughout the study until 30 days after treatment discontinuation ]
  • Dose interruptions, reductions and dose intensity [ Time Frame: Continuously throughout the study until 30 days after treatment discontinuation ]


Original Primary Outcome:

  • Incidence of dose limiting toxicities (DLTs) (Dose escalation only) [ Time Frame: Cycle 1 in dose escalation ]
    cycle = 28 days
  • Incidence and severity of adverse events and serious adverse events, including changes in laboratory parameters, vital signs and ECGs graded as per NCI CTCAE version 4.03 (All patients) [ Time Frame: Continuously throughout the study until 30 days after treatment discontinuation ]
  • Dose interruptions, reductions and dose intensity [ Time Frame: Continously throughtout the study until 30 days after treatment discontinutation ]


Current Secondary Outcome:

  • Overall response rate (ORR) per RECIST version 1.1 criteria [ Time Frame: From baseline, every 2 cycles until cycle 11, then every 3 cycles afterwards until disease progression or withdrawal of consent up to 12 months ]
  • Plasma LXS196 concentration-time profiles [ Time Frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1 ]
  • Modulation of signaling molecules downstream of protein kinase C inhibitor [ Time Frame: Baseline and Cycle 1 Day 15 ]
  • Progression free survival (PFS) per RECIST version 1.1 criteria [ Time Frame: From baseline, every 2 cycles until cycle 11, then every 3 cycles afterwards until disease progression or withdrawal of consent up to 12 months ]
  • Plasma PK parameters of LXS196:AUC [ Time Frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1 ]
  • Plasma PK parameters of LXS196: Cmax [ Time Frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1 ]
  • Plasma PK parameters of LXS196: Tmax [ Time Frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1 ]
  • Plasma PK parameters of LXS196: t1/2 [ Time Frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1 ]
  • Plasma PK parameters of LXS196: Racc [ Time Frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1 ]


Original Secondary Outcome: Same as current

Information By: Novartis

Dates:
Date Received: November 6, 2015
Date Started: February 1, 2016
Date Completion: March 24, 2019
Last Updated: April 24, 2017
Last Verified: April 2017