A Safety, Pharmacokinetic, Pharmacodynamic and Anti-Tumour Study of PF-06873600 as a Single Agent and in Combination With Endocrine Therapy

Official Title

Phase 1/2A dose escalation and expansion study evaluating safety, tolerability, pharmacokinetic, pharmacodynamics and anti-tumor activity of PF-06873600 as a single agent and in combination with endocrine therapy

Summary:

Open-label, multi-centre, non-randomized, multiple dose, safety, tolerability, pharmacokinetic, and pharmacodynamics and clinical activity study of PF-06873600 administered as a single agent and then in combination with endocrine therapy. The study contains two parts, a Part 1 single agent dose escalation and combination endocrine therapy dose finding component and a Part 2 dose expansion in combination with endocrine therapy.

Trial Description

Primary Outcome:

  • Number of patients with dose limiting toxicities in the Dose Escalation portion
  • Safety and Tolerability as assessed by adverse event monitoring for patients enrolled in the Dose Escalation, Dose Finding and Dose Expansion Arms
  • Safety and Tolerability as assessed through monitoring of hematology and blood chemistry laboratory assessments for patients enrolled in the Dose Escalation, Dose Finding Portion and the Dose Expansion Arms
  • Safety and Tolerability as assessed through vital sign monitoring for patients enrolled in the Dose Escalation, Dose Finding Portion and the Dose Expansion Arms
  • Safety and Tolerability as assessed by heart rate corrected QT interval for patients enrolled in the Dose Escalation, Dose Finding Portion and the Dose Expansion Arms
  • Objective Response Rate (ORR) observed in patients in the Dose Expansion Arms
  • Safety and Tolerability as assessed through monitoring of coagulation laboratory assessments for patients enrolled in the Dose Escalation, Dose Finding Portion and the Dose Expansion Arms
  • Safety and Tolerability as assessed through monitoring of urinalysis laboratory assessments for patients enrolled in the Dose Escalation, Dose Finding Portion and the Dose Expansion Arms
Secondary Outcome:
  • Single Dose: Maximal concentration (Cmax) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
  • Single Dose: Plasma concentrations with and without food observed in patients enrolled in one of the single agent Dose Expansion Arms
  • Single Dose: Time to Maximum Plasma Concentration (Tmax) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
  • Single Dose: Area Under the Plasma Concentration Versus Time Curve from Time Zero to the Last Sampling Time Point Within the Dose Interval (AUClast) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
  • Single Dose: Area Under the Plasma Concentration Versus Time Curve from Time Zero Extrapolated to Infinity (AUCinf) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
  • Single Dose: Apparent Oral Plasma Clearance (CL/F) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
  • Single Dose: Apparent Volume of Distribution (Vz/F) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
  • Single Dose: Terminal Elimination Half-Life (t1/2) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
  • Multiple Dose: Steady State Maximal Concentration (Css,max) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
  • Multiple Dose: Time to Maximum Plasma Concentration at Steady State (Tss,max) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
  • Multiple Dose: Area Under the Plasma Concentration Versus Time Curve Within One Dose Interval (AUCss,t) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
  • Multiple Dose: Steady State Minimum Plasma Concentration (Css,min) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
  • Multiple Dose: Steady State Apparent Oral Plasma Clearance (CLss/F) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
  • Multiple Dose: Apparent Volume of Distribution at Steady State (Vss/F) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
  • Multiple Dose: Terminal Elimination Half-Life (t1/2) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
  • Multiple Dose: Accumulation Ratio (Rac (AUCss,t /AUCsd,t)) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
  • Tumour Response observed in patients in Dose Escalation and Dose Finding portion
  • Duration of Response (DOR) in patients enrolled in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
  • Progression Free Survival (PFS) observed in patients in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
  • Time to Progression (TTP) observed in patients enrolled in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
  • Overall Survival observed in patients enrolled in the Dose Expansion Arms
  • Pharmacodynamic (PD) biomarkers (pRb and Ki67) in tumour tissue in patients enrolled in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
This is a Phase 1/2a, open-label, multi-centre, non-randomized, multiple dose, safety, tolerability, pharmacokinetic, and pharmacodynamic study of PF-06873600 administered as a single agent in sequential dose levels and then in combination with endocrine therapy. In Part 1A and Part 1C, successive cohorts of patients will receive escalating doses of PF-06873600 and then in dose finding (Part 1B) with PF-06873600 in combination with endocrine therapy (ET). This study contains 2 parts, dose escalation with single agent (Part 1A and 1C) and then dose finding with PF-06873600 in combination with endocrine therapy (Part 1B) followed by dose expansion arms of PF-06873600 in combination with endocrine therapy (Part 2).

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

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