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Trial record 1 of 1 for:    NCT03519178
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A Safety, Pharmacokinetic, Pharmacodynamic and Anti-Tumor Study of PF-06873600 as a Single Agent and in Combination With Endocrine Therapy

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ClinicalTrials.gov Identifier: NCT03519178
Recruitment Status : Recruiting
First Posted : May 8, 2018
Last Update Posted : August 13, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE February 22, 2018
First Posted Date  ICMJE May 8, 2018
Last Update Posted Date August 13, 2019
Actual Study Start Date  ICMJE March 7, 2018
Estimated Primary Completion Date October 29, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 25, 2018)
  • Number of patients with dose limiting toxicities in the Dose Escalation portion [ Time Frame: up to 28 days ]
  • Safety and Tolerability as assessed by adverse event monitoring for patients enrolled in the Dose Escalation, Dose Finding and Dose Expansion Arms [ Time Frame: Weekly during Cycle 1 (each cycle is 28 days) and 2 and then every 28 days through study completion, up to approximately 24 months ]
    Adverse events
  • 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 [ Time Frame: Weekly during Cycle 1 (each cycle is 28 days) and 2 and then every 28 days through study completion, up to approximately 24 months ]
    safety laboratory abnormalities
  • Safety and Tolerability as assessed through vital sign monitoring for patients enrolled in the Dose Escalation, Dose Finding Portion and the Dose Expansion Arms [ Time Frame: Weekly during Cycle 1 (each cycle is 28 days) and 2 and then every 28 days through study completion, up to approximately 24 months ]
    vital signs
  • 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 [ Time Frame: Day 1, 8 and 15 of Cycle 1 (each cycle is 28 days) and then every 28 days through study completion, up to approximately 24 months ]
    heart rate corrected QT interval
  • Objective Response Rate (ORR) observed in patients in the Dose Expansion Arms [ Time Frame: baseline up to approximately 24 months ]
    Number of patients in each Arm. ORR (number of patients with a Partial Response (PR) + Complete Response (CR) relative to the number of evaluable patients
  • 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 [ Time Frame: Day 1 of Cycle 1 (each cycle is 28 days) and 2 and at completion, approximately 24 months ]
    safety laboratory abnormalities
  • 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 [ Time Frame: Screening and at completion, approximately 24 months ]
    safety laboratory abnormalities
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03519178 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 25, 2018)
  • 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 ]
    Pharmacokinetic (PK) assessments for PF-06873600
  • 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) ]
  • 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 ]
    Pharmacokinetic (PK) assessments for PF-06873600
  • 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 ]
    Pharmacokinetic (PK) assessments for PF-06873600
  • 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 ]
    Pharmacokinetic (PK) assessments for PF-06873600
  • 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 ]
    Pharmacokinetic (PK) assessments for PF-06873600
  • 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 ]
    Pharmacokinetic (PK) assessments for PF-06873600
  • 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 ]
    Pharmacokinetic (PK) assessments for PF-06873600
  • 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 ]
    Pharmacokinetic (PK) assessments for PF-06873600
  • 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 ]
    Pharmacokinetic (PK) assessments for PF-06873600
  • 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 ]
    Pharmacokinetic (PK) assessments for PF-06873600
  • 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 ]
    Pharmacokinetic (PK) assessments for PF-06873600
  • 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 ]
    Pharmacokinetic (PK) assessments for PF-06873600
  • 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 ]
    Pharmacokinetic (PK) assessments for PF-06873600
  • 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 ]
    Pharmacokinetic (PK) assessments for PF-06873600
  • 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 ]
    Pharmacokinetic (PK) assessments for PF-06873600
  • Tumor Response observed in patients in Dose Escalation and Dose Finding portion [ Time Frame: baseline up to approximately 24 months ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Overall Survival observed in patients enrolled in the Dose Expansion Arms [ Time Frame: baseline up to approximately 24 months ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety, Pharmacokinetic, Pharmacodynamic and Anti-Tumor Study of PF-06873600 as a Single Agent and in Combination With Endocrine Therapy
Official Title  ICMJE 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
Brief Summary 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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HR+ HER2- Metastatic Breast Cancer, Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer, Triple Negative Breast Cancer, Male Breast Cancer
Intervention  ICMJE
  • Drug: PF-06873600
    PF-06873600 tablet for oral dosing
  • Drug: Endocrine Therapy 1
    Endocrine Therapy 1
  • Drug: Endocrine Therapy 2
    Endocrine Therapy 2
Study Arms  ICMJE
  • Experimental: Dose Escalation
    Single Agent Dose Escalation
    Intervention: Drug: PF-06873600
  • Experimental: Dose Finding Endocrine Therapy 1 Combination
    Part 1B PF-06873600 plus Endocrine Therapy 1
    Interventions:
    • Drug: PF-06873600
    • Drug: Endocrine Therapy 1
  • Experimental: Dose Finding Endocrine Therapy 2 Combination
    Part 1B PF-06873600 plus Endocrine Therapy 2
    Interventions:
    • Drug: PF-06873600
    • Drug: Endocrine Therapy 2
  • Experimental: Dose Expansion Arm A
    PF-06873600 as a Single Agent
    Intervention: Drug: PF-06873600
  • Experimental: Dose Expansion Arm B
    PF-06873600 as a Single Agent in Various Tumor Types
    Intervention: Drug: PF-06873600
  • Experimental: Dose Expansion Arm C
    PF-06873600 in Combination with Endocrine Therapy 1
    Interventions:
    • Drug: PF-06873600
    • Drug: Endocrine Therapy 1
  • Experimental: Dose Expansion Arm D
    PF-06873600 in Combination with Endocrine Therapy 1
    Interventions:
    • Drug: PF-06873600
    • Drug: Endocrine Therapy 1
  • Experimental: Dose Expansion Arm E
    PF-06873600 in Combination with Endocrine Therapy 2
    Interventions:
    • Drug: PF-06873600
    • Drug: Endocrine Therapy 2
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 25, 2018)
220
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 29, 2022
Estimated Primary Completion Date October 29, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03519178
Other Study ID Numbers  ICMJE C3661001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP