Clinical trial NCT03519178: A Study of PF-06873600 in People With Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: HR+ HER2- Metastatic Breast Cancer, Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer, Triple Negative Breast Cancer, Male Breast Cancer
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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-05-08
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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 for the first 2 cycles and every cycle thereafter.

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).

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 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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs) - Part 1
timeFrame: Cycle 1 (within 28 days after the first dose of study intervention)
measure: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) - Part 1 + Part 2
timeFrame: Day 1 up to 28 days after the last dose of study intervention, up to approximately 24 months
measure: Number of Participants With Worst Post-Baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) Grade: Part 1 + Part 2
timeFrame: Day 1 up to 28 days after the last dose of study intervention, up to approximately 24 months
measure: Number of Participants With Worst Post-Baseline Chemistry Results Based on Common Terminology Criteria for Adverse Events (CTCAE) Grade: Part 1 + Part 2
timeFrame: Day 1 up to 28 days after the last dose of study intervention, up to approximately 24 months
measure: Number of Participants With Post-Baseline Vital Sign Abnormalities Meeting Pre-Defined Categorization - Part 1 + Part 2
timeFrame: Day 1 up to 28 days after the last dose of study intervention, up to approximately 24 months
measure: Number of Participants With Post-Baseline Electrocardiogram (ECG) Changes Meeting Pre-Defined Categorization - Part 1 + Part 2
timeFrame: Day 1 up to 28 days after the last dose of study intervention, up to approximately 24 months
measure: Overall Response Rate (ORR): Part 2
timeFrame: From the start of the treatment until disease/clinical progression or death or early study discontinuation, whichever happened earlier (approximately up to 24 months)
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of PF-06873600 Following a Single Oral Dose of Study Intervention on Cycle 1 Day 1 - Part 1 + Part 2
timeFrame: Part 1: pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 12 hours post-dose on Cycle 1 Day 1 (C1D1); Part 2: pre-dose, 1, 2, 4, 6 hours post-dose on C1D1
measure: Time to Reach Cmax at Steady State (Tmax) of PF-06873600 Following a Single Oral Dose of Study Intervention on Cycle 1 Day 1 - Part 1 + Part 2
timeFrame: Part 1: pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 12 hours post-dose on C1D1; Part 2: pre-dose, 1, 2, 4, 6 hours post-dose on C1D1
measure: Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-06873600 Following a Single Oral Dose of Study Intervention on Cycle 1 Day 1 - Part 1
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 12 hours post-dose on C1D1
measure: Area Under the Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06873600 Following a Single Oral Dose of Study Intervention on Cycle 1 Day 1 - Part 1
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 12 hours post-dose on C1D1
measure: Apparent Clearance (CL/F) of PF-06873600 Following a Single Oral Dose of Study Intervention on Cycle 1 Day 1 - Part 1
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 12 hours post-dose on C1D1
measure: Apparent Volume of Distribution (Vz/F) of PF-06873600 Following a Single Oral Dose of Study Intervention on Cycle 1 Day 1 - Part 1
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 12 hours post-dose on C1D1
measure: Terminal Half-life (t1/2) of PF-06873600 Following a Single Oral Dose of Study Intervention on Cycle 1 Day 1 - Part 1
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 12 hours post-dose on C1D1
measure: Steady State Maximum Concentration (Css,Max) of PF-06873600 Following Multiple Doses of Study Intervention on Cycle 1 Day 15 - Part 1 + Part 2
timeFrame: Part 1: pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 12 hours post-dose on C1D15; Part 2: pre-dose, 1, 2, 4, 6 hours post-dose on C1D15
measure: Time to Maximum Plasma Concentration at Steady State (Tss,Max) of PF-06873600 Following Multiple Doses of Study Intervention on Cycle 1 Day 15 - Part 1 + Part 2
timeFrame: Part 1: pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 12 hours post-dose on C1D15; Part 2: pre-dose, 1, 2, 4, 6 hours post-dose on C1D15
measure: Steady State Minimum Plasma Concentration (Css,Min) of PF-06873600 Following Multiple Doses of Study Intervention on Cycle 1 Day 15 - Part 1 + Part 2
timeFrame: Part 1: pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 12 hours post-dose on C1D15; Part 2: pre-dose, 1, 2, 4, 6 hours post-dose on C1D15
measure: Steady-State Area Under the Plasma Concentration Versus Time Curve Within One Dose Interval (AUCss,Tau) of PF-06873600 Following Multiple Doses of Study Intervention on Cycle 1 Day 15 - Part 1
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 12 hours post-dose on C1D15
measure: Steady-State Apparent Oral Plasma Clearance (CLss/F) of PF-06873600 Following Multiple Doses of Study Intervention on Cycle 1 Day 15 - Part 1
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 12 hours post-dose on C1D15
measure: Apparent Volume of Distribution at Steady State (Vss/F) of PF-06873600 Following Multiple Doses of Study Intervention on Cycle 1 Day 15 - Part 1
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 12 hours post-dose on C1D15
measure: Accumulation Ratio Based on AUC (Rac) of PF-06873600 Following Multiple Doses of Study Intervention on Cycle 1 Day 15 - Part 1
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 12 hours post-dose on C1D15
measure: Accumulation Ratio Based on Cmax (Observed) (Rac,Cmax) of PF-06873600 Following Multiple Doses of Study Intervention on Cycle 1 Day 15 - Part 2
timeFrame: Pre-dose, 1, 2, 4, 6 hours post-dose on C1D15
measure: Pharmacodynamic (PD) Biomarker Phospho-retinoblastoma Protein (pRb) in Tumor Tissue in Participants - Part 1 + Part 2
timeFrame: Screening and Cycle 2 Day 1
measure: PD Biomarker Ki67 in Tumor Tissue in Participants - Part 1 + Part 2
timeFrame: Screening and Cycle 2 Day 1
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Birmingham
country: United States
facility: University Of Alabama at Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: HonorHealth
state: Arizona
city: Scottsdale
country: United States
facility: Virginia G. Piper Cancer Center Pharmacy
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Rogers
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Springdale
country: United States
facility: Highlands Oncology
state: Arkansas
city: Glendale
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Long Beach
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Investigational Drugs Pharmacy
state: California
city: Santa Ana
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology - Parkside
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology - Santa Monica
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
state: Colorado
city: Lone Tree
country: United States
facility: UCHealth Lone Tree Medical Center
state: Colorado
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Long Island City
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute-Pharmacy
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC
state: Texas
city: Federal Way
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
city: Gig Harbor
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
city: Puyallup
country: United States
facility: Rainier Hematology-Oncology PC
state: Washington
city: Puyallup
country: United States
facility: Rainier Hematology-Oncology, PC
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
city: Dobrich
country: Bulgaria
facility: Multiprofile Hospital of Active Treatment - Dobrich AD
city: Haskovo
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Oncology - Haskovo EOOD
city: Plovdiv
country: Bulgaria
facility: Complex Oncology Center -Plovdiv
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Yokohama
country: Japan
facility: Kanagawa cancer center
state: Kanagawa
city: Pushkin
country: Russian Federation
facility: Private Medical Institution "Euromedservice"
state: Saint-petersburg
city: Omsk
country: Russian Federation
facility: BIH of Omsk Region "Clinical Oncological Dispensary"
city: Omsk
country: Russian Federation
facility: BIH of Omsk Region "Clinical Oncological Dispensary"
city: Saint-Petersburg
country: Russian Federation
facility: LLC "Medicina Severnoy Stolitsy"
city: Saint-Petersburg
country: Russian Federation
facility: LLC "Severo-Zapadny Medical Center"
city: Dnipro
country: Ukraine
facility: Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council, "Dnipro State Me
state: Dnipropetrovska Oblast
city: Kharkiv
country: Ukraine
facility: Kharkiv Regional Specialized Dispensary of Radiation Protection of the Population
state: Kharkivska Oblast
city: Kyiv
country: Ukraine
facility: Communal nonprofit enterprise "Kyiv City Clinical Oncology Center" of Executive Body of Kyiv City
city: Lviv
country: Ukraine
facility: Communal noncommercial enterprise of Lviv regional council "Lviv oncological regional therapeutical
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: