A Study of PF-06873600 in People With Cancer

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

The purpose of this clinical trial is to learn about the safety and effects of study medicine (PF-06873600) when taken alone or with hormone therapy by people with cancer.

People may be able to participate in this study if they have the following types of cancer: Hormone Receptor positive (HR+) breast cancer; Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer that is advanced or metastatic (spread to other parts of the body); triple negative breast cancer; epithelial ovarian cancer; fallopian tube cancer; or primary peritoneal cancer.

All participants in this study will receive the study medicine by mouth, 1 to 2 times a day at home. The dose of the study medicine may be changed during the study.

Some participants will also receive hormone therapy. The hormone therapy will be either letrozole by mouth once a day at home, or fulvestrant as a shot into the muscle. Fulvestrant will be given every two weeks at the study clinic for the first month, and then once a month after that.

Participants will take part in this study for at least 7 to 8 months, depending on how they respond to the therapy. During this time participants will visit the study clinic once a week.

Study Overview

• Status: Active, not recruiting
• Conditions: HR+ HER2- Metastatic Breast Cancer, Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer, Triple Negative Breast Cancer, Male Breast Cancer
• Intervention / Treatment: Drug: PF-06873600; Drug: Endocrine Therapy 1; Drug: Endocrine Therapy 2

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 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).

• Study Type: Interventional
• Enrollment (Actual): 155
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Dobrich, Bulgaria, 9300
    • Multiprofile Hospital of Active Treatment - Dobrich AD
  • Haskovo, Bulgaria, 6300
    • Specialized Hospital for Active Treatment of Oncology - Haskovo EOOD
  • Plovdiv, Bulgaria, 4000
    • Complex Oncology Center -Plovdiv
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 2418515
      • Kanagawa Cancer Center
• Russian Federation
  • Omsk, Russian Federation, 644013
    • BIH of Omsk Region "Clinical Oncological Dispensary"
  • Omsk, Russian Federation, 644046
    • BIH of Omsk Region "Clinical Oncological Dispensary"
  • Saint-Petersburg, Russian Federation, 191025
    • LLC "Medicina Severnoy Stolitsy"
  • Saint-Petersburg, Russian Federation, 192007
    • LLC "Severo-Zapadny Medical Center"
  • Saint-petersburg
    • Pushkin, Saint-petersburg, Russian Federation, 196603
      • Private medical institution "Euromedservice"
• Ukraine
  • Kyiv, Ukraine, 03115
    • Communal nonprofit enterprise "Kyiv City Clinical Oncology Center" of Executive Body of Kyiv City
  • Lviv, Ukraine, 79031
    • Communal noncommercial enterprise of Lviv regional council "Lviv oncological regional therapeutica
  • Dnipropetrovska Oblast
    • Dnipro, Dnipropetrovska Oblast, Ukraine, 49102
      • Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council, "Dnipro State Me
  • Kharkivska Oblast
    • Kharkiv, Kharkivska Oblast, Ukraine, 61166
      • Kharkiv Regional Specialized Dispensary of Radiation Protection of the Population
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth
    • Scottsdale, Arizona, United States, 85258
      • Virginia G. Piper Cancer Center Pharmacy
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
    • Rogers, Arkansas, United States, 72758
      • Highlands Oncology Group
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology Group
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology
  • California
    • Glendale, California, United States, 91204
      • The Oncology Institute of Hope and Innovation
    • Long Beach, California, United States, 90805
      • The Oncology Institute of Hope and Innovation
    • San Francisco, California, United States, 94143
      • UCSF Helen Diller Family Comprehensive Cancer Center
    • San Francisco, California, United States, 94158
      • UCSF Investigational Drugs Pharmacy
    • Santa Ana, California, United States, 92705
      • The Oncology Institute of Hope and Innovation
    • Santa Monica, California, United States, 90404
      • UCLA Hematology/Oncology - Santa Monica
    • Santa Monica, California, United States, 90404
      • UCLA Hematology/Oncology - Parkside
    • Whittier, California, United States, 90602
      • The Oncology Institute of Hope and Innovation
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
    • Lone Tree, Colorado, United States, 80124
      • UCHealth Lone Tree Medical Center
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
  • New York
    • Long Island City, New York, United States, 11101
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37203
      • The Sarah Cannon Research Institute
    • Nashville, Tennessee, United States, 37203
      • The Sarah Cannon Research Institute-Pharmacy
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Md Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics, LLC
  • Washington
    • Federal Way, Washington, United States, 98003
      • NorthWest Medical Specialties, PLLC
    • Gig Harbor, Washington, United States, 98332
      • NorthWest Medical Specialties, PLLC
    • Puyallup, Washington, United States, 98373
      • Rainier Hematology-Oncology, PC
    • Puyallup, Washington, United States, 98373
      • Rainier Hematology-Oncology PC
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center
    • Tacoma, Washington, United States, 98405
      • NorthWest Medical Specialties, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 1B and Part 2 only)

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Single Agent Dose Escalation	Drug: PF-06873600; PF-06873600 tablet for oral dosing
Experimental: Dose Finding Endocrine Therapy 1 Combination; Part 1B PF-06873600 plus Endocrine Therapy 1	Drug: PF-06873600; PF-06873600 tablet for oral dosing; Drug: Endocrine Therapy 1; Endocrine Therapy 1
Experimental: Dose Finding Endocrine Therapy 2 Combination; Part 1B PF-06873600 plus Endocrine Therapy 2	Drug: PF-06873600; PF-06873600 tablet for oral dosing; Drug: Endocrine Therapy 2; Endocrine Therapy 2
Experimental: Dose Expansion Arm A; PF-06873600 as a Single Agent	Drug: PF-06873600; PF-06873600 tablet for oral dosing
Experimental: Dose Expansion Arm B; PF-06873600 as a Single Agent in Various Tumor Types	Drug: PF-06873600; PF-06873600 tablet for oral dosing
Experimental: Dose Expansion Arm C; PF-06873600 in Combination with Endocrine Therapy 1	Drug: PF-06873600; PF-06873600 tablet for oral dosing; Drug: Endocrine Therapy 1; Endocrine Therapy 1
Experimental: Dose Expansion Arm D; PF-06873600 in Combination with Endocrine Therapy 1	Drug: PF-06873600; PF-06873600 tablet for oral dosing; Drug: Endocrine Therapy 1; Endocrine Therapy 1
Experimental: Dose Expansion Arm E; PF-06873600 in Combination with Endocrine Therapy 2	Drug: PF-06873600; PF-06873600 tablet for oral dosing; Drug: Endocrine Therapy 2; Endocrine Therapy 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with dose limiting toxicities in the Dose Escalation portion		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	Adverse events	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 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 laboratory abnormalities	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 and Tolerability as assessed through vital sign monitoring for patients enrolled in the Dose Escalation, Dose Finding Portion and the Dose Expansion Arms	vital signs	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 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	heart rate corrected QT interval	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
Objective Response Rate (ORR) observed in patients in the Dose Expansion Arms	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	baseline up to approximately 24 months
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 laboratory abnormalities	Day 1 of Cycle 1 (each cycle is 28 days) and 2 and at completion, approximately 24 months
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	safety laboratory abnormalities	Screening and at completion, approximately 24 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2018
• Primary Completion (Actual): April 5, 2023
• Study Completion (Estimated): November 28, 2024

Study Registration Dates

• First Submitted: February 22, 2018
• First Submitted That Met QC Criteria: April 25, 2018
• First Posted (Actual): May 8, 2018

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Fallopian tube cancer; Triple negative breast cancer (TNBC); Advanced breast cancer; Goserelin; Metastatic breast cancer (MBC); CDK4/6 inhibitor; Epithelial ovarian cancer (EOC); Leuprolide acetate; 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; Primary peritoneal cancer (PPC); Endocrine Therapy (ET); Measurable disease; Luteinizing Hormone Releasing Hormone (LHRH) Agonist
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Breast Diseases; Fallopian Tube Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Breast Neoplasms; Ovarian Neoplasms; Fallopian Tube Neoplasms; Triple Negative Breast Neoplasms; Breast Neoplasms, Male
• Other Study ID Numbers: C3661001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No