Clinical Trials /

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

NCT03519178

Description:

Open-label, multi-center, 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 as both a single agent and in combination with endocrine therapy.

Related Conditions:
  • Breast Carcinoma
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Safety, Pharmacokinetic, Pharmacodynamic and Anti-Tumor 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

Clinical Trial IDs

  • ORG STUDY ID: C3661001
  • NCT ID: NCT03519178

Conditions

  • HR+ HER2- Metastatic Breast Cancer, Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer, Triple Negative Breast Cancer, Male Breast Cancer

Interventions

DrugSynonymsArms
PF-06873600Dose Escalation
Endocrine Therapy 1Dose Finding Endocrine Therapy 1 Combination
Endocrine Therapy 2Dose Finding Endocrine Therapy 2 Combination

Purpose

Open-label, multi-center, 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 as both a single agent and in combination with endocrine therapy.

Detailed Description

      This is a Phase 1/2a, open-label, multi-center, 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, 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 then dose finding
      with PF-06873600 in combination with endocrine therapy (Part 1B) followed by dose expansion
      arms as a single agent and PF-06873600 in combination with endocrine therapy (Part 2).
    

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalSingle Agent Dose Escalation
  • PF-06873600
Dose Finding Endocrine Therapy 1 CombinationExperimentalPart 1B PF-06873600 plus Endocrine Therapy 1
  • PF-06873600
  • Endocrine Therapy 1
Dose Finding Endocrine Therapy 2 CombinationExperimentalPart 1B PF-06873600 plus Endocrine Therapy 2
  • PF-06873600
  • Endocrine Therapy 2
Dose Expansion Arm AExperimentalPF-06873600 as a Single Agent
  • PF-06873600
Dose Expansion Arm BExperimentalPF-06873600 as a Single Agent in Various Tumor Types
  • PF-06873600
Dose Expansion Arm CExperimentalPF-06873600 in Combination with Endocrine Therapy 1
  • PF-06873600
  • Endocrine Therapy 1
Dose Expansion Arm DExperimentalPF-06873600 in Combination with Endocrine Therapy 1
  • PF-06873600
  • Endocrine Therapy 1
Dose Expansion Arm EExperimentalPF-06873600 in Combination with Endocrine Therapy 2
  • PF-06873600
  • Endocrine Therapy 2

Eligibility Criteria

        Inclusion Criteria:

          -  Have a diagnosis of Hormone Receptor Positive (HR+), Human Epidermal Growth Factor
             Receptor 2 Negative (HER2-) breast cancer

             • Prior combined CDK 4/6 inhibitor and endocrine therapy and 1 or 2 prior lines of
             chemotherapy

          -  Have a diagnosis of metastatic triple negative breast cancer (TNBC)

             • Up to 1-2 prior lines of chemotherapy

          -  Have a diagnosis of advanced platinum resistant epithelial ovarian cancer
             (EOC)/fallopian tube cancer/primary peritoneal cancer (PPC)

             • Up to 2-3 prior lines of therapy

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1

          -  Measurable disease or non-measurable disease and refractory to or intolerant of
             existing therapies (Part 1)

          -  Measurable disease as defined by RECIST 1.1 is required (Part 2)

        Exclusion Criteria:

          -  Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases

          -  Other active malignancy within 3 years prior to randomization, except for adequately
             treated basal cell or squamous cell skin cancer, or carcinoma in situ

          -  Major surgery or radiation within 4 weeks prior to study entry

          -  Last anti-cancer treatment within 2 weeks prior to study entry

          -  Participation in other studies involving investigational drug(s) within 4 weeks prior
             to study entry

          -  Pregnant or breastfeeding female patients

          -  Active inflammatory gastrointestinal (GI) disease, known diverticular disease or
             previous gastric resection or lap band surgery including impairment of gastro
             intestinal function or GI disease
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients with dose limiting toxicities in the Dose Escalation portion
Time Frame:up to 28 days
Safety Issue:
Description:Adverse events

Secondary Outcome Measures

Measure:Single Dose: Maximal concentration (Cmax) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
Time Frame:Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-06873600
Measure:Single Dose: Plasma concentrations with and without food observed in patients enrolled in one of the single agent Dose Expansion Arms
Time Frame:7 days prior to Cycle 1 (each cycle is 28 days) and in Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:
Measure:Single Dose: Time to Maximum Plasma Concentration (Tmax) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
Time Frame:Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-06873600
Measure: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
Time Frame:Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-06873600
Measure: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
Time Frame:Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-06873600
Measure:Single Dose: Apparent Oral Plasma Clearance (CL/F) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
Time Frame:Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-06873600
Measure:Single Dose: Apparent Volume of Distribution (Vz/F) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
Time Frame:Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-06873600
Measure:Single Dose: Terminal Elimination Half-Life (t1/2) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
Time Frame:Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-06873600
Measure:Multiple Dose: Steady State Maximal Concentration (Css,max) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
Time Frame:Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-06873600
Measure:Multiple Dose: Time to Maximum Plasma Concentration at Steady State (Tss,max) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
Time Frame:Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-06873600
Measure: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
Time Frame:Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-06873600
Measure:Multiple Dose: Steady State Minimum Plasma Concentration (Css,min) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
Time Frame:Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-06873600
Measure:Multiple Dose: Steady State Apparent Oral Plasma Clearance (CLss/F) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
Time Frame:Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-06873600
Measure:Multiple Dose: Apparent Volume of Distribution at Steady State (Vss/F) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
Time Frame:Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-06873600
Measure:Multiple Dose: Terminal Elimination Half-Life (t1/2) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
Time Frame:Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-06873600
Measure:Multiple Dose: Accumulation Ratio (Rac (AUCss,t /AUCsd,t)) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
Time Frame:Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-06873600
Measure:Tumor Response observed in patients in Dose Escalation and Dose Finding portion
Time Frame:baseline up to approximately 24 months
Safety Issue:
Description:
Measure:Duration of Response (DOR) in patients enrolled in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
Time Frame:baseline up to approximately 24 months
Safety Issue:
Description:
Measure:Progression Free Survival (PFS) observed in patients in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
Time Frame:baseline up to approximately 24 months
Safety Issue:
Description:
Measure:Time to Progression (TTP) observed in patients enrolled in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
Time Frame:baseline up to approximately 24 months
Safety Issue:
Description:
Measure:Overall Survival observed in patients enrolled in the Dose Expansion Arms
Time Frame:baseline up to approximately 24 months
Safety Issue:
Description:
Measure:Pharmacodynamic (PD) biomarkers (pRb and Ki67) in tumor tissue in patients enrolled in the Dose Escalation and Dose Finding portion and Dose Expansion Arms
Time Frame:Screening, Cycle 1 (each cycle is 28 days), Cycle 2 and 3 and at the study completion visit, up to approximately 24 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Pfizer

Trial Keywords

  • Hormone Receptor (HR) Positive Breast Cancer
  • Estrogen receptor (ER) positive
  • Progesterone receptor (PR) positive
  • Cyclin-dependent kinase (CDK)
  • Human epidermal growth factor receptor 2 (HER2) negative
  • Advanced breast cancer
  • Metastatic breast cancer (MBC)
  • Triple negative breast cancer (TNBC)
  • Epithelial ovarian cancer (EOC)
  • Fallopian tube cancer
  • Primary peritoneal cancer (PPC)
  • CDK4/6 inhibitor
  • Endocrine Therapy (ET)
  • Measurable disease
  • Luteinizing Hormone Releasing Hormone (LHRH) Agonist
  • Goserelin
  • Leuprolide acetate

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