HR+ HER2- Metastatic Breast Cancer, Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer, Triple Negative Breast Cancer, Male Breast Cancer Clinical Trial
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
| Verified date | December 2023 |
| Source | Pfizer |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 155 |
| Est. completion date | November 28, 2024 |
| Est. primary completion date | April 5, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Bulgaria | Multiprofile Hospital of Active Treatment - Dobrich AD | Dobrich | |
| Bulgaria | Specialized Hospital for Active Treatment of Oncology - Haskovo EOOD | Haskovo | |
| Bulgaria | Complex Oncology Center -Plovdiv | Plovdiv | |
| Canada | McGill University Health Centre | Montreal | Quebec |
| Japan | National Cancer Center Hospital East | Kashiwa | Chiba |
| Japan | Kanagawa cancer center | Yokohama | Kanagawa |
| Russian Federation | BIH of Omsk Region "Clinical Oncological Dispensary" | Omsk | |
| Russian Federation | BIH of Omsk Region "Clinical Oncological Dispensary" | Omsk | |
| Russian Federation | Private Medical Institution "Euromedservice" | Pushkin | Saint-petersburg |
| Russian Federation | LLC "Medicina Severnoy Stolitsy" | Saint-Petersburg | |
| Russian Federation | LLC "Severo-Zapadny Medical Center" | Saint-Petersburg | |
| Ukraine | Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council, "Dnipro State Me | Dnipro | Dnipropetrovska Oblast |
| Ukraine | Kharkiv Regional Specialized Dispensary of Radiation Protection of the Population | Kharkiv | Kharkivska Oblast |
| Ukraine | Communal nonprofit enterprise "Kyiv City Clinical Oncology Center" of Executive Body of Kyiv City | Kyiv | |
| Ukraine | Communal noncommercial enterprise of Lviv regional council "Lviv oncological regional therapeutica | Lviv | |
| United States | University of Colorado Hospital - Anschutz Cancer Pavilion (ACP) | Aurora | Colorado |
| United States | University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP) | Aurora | Colorado |
| United States | University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP) | Aurora | Colorado |
| United States | University of Alabama at Birmingham | Birmingham | Alabama |
| United States | University Of Alabama at Birmingham | Birmingham | Alabama |
| United States | Brigham & Women's Hospital | Boston | Massachusetts |
| United States | Dana Farber Cancer Institute | Boston | Massachusetts |
| United States | Dana-Farber Cancer Institute | Boston | Massachusetts |
| United States | Massachusetts General Hospital | Boston | Massachusetts |
| United States | Highlands Oncology Group | Fayetteville | Arkansas |
| United States | Northwest Medical Specialties, PLLC | Federal Way | Washington |
| United States | Holy Cross Hospital | Fort Lauderdale | Florida |
| United States | Northwest Medical Specialties, PLLC | Gig Harbor | Washington |
| United States | The Oncology Institute of Hope and Innovation | Glendale | California |
| United States | The University of Texas MD Anderson Cancer Center | Houston | Texas |
| United States | UCHealth Lone Tree Medical Center | Lone Tree | Colorado |
| United States | The Oncology Institute of Hope and Innovation | Long Beach | California |
| United States | Memorial Sloan Kettering Cancer Center | Long Island City | New York |
| United States | Tennessee Oncology, PLLC | Nashville | Tennessee |
| United States | The Sarah Cannon Research Institute | Nashville | Tennessee |
| United States | The Sarah Cannon Research Institute-Pharmacy | Nashville | Tennessee |
| United States | Memorial Sloan Kettering Cancer Center | New York | New York |
| United States | Rainier Hematology-Oncology PC | Puyallup | Washington |
| United States | Rainier Hematology-Oncology, PC | Puyallup | Washington |
| United States | Highlands Oncology Group | Rogers | Arkansas |
| United States | South Texas Accelerated Research Therapeutics, LLC | San Antonio | Texas |
| United States | UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco | California |
| United States | UCSF Investigational Drugs Pharmacy | San Francisco | California |
| United States | The Oncology Institute of Hope and Innovation | Santa Ana | California |
| United States | UCLA Hematology/Oncology - Parkside | Santa Monica | California |
| United States | UCLA Hematology/Oncology - Santa Monica | Santa Monica | California |
| United States | HonorHealth | Scottsdale | Arizona |
| United States | HonorHealth Research Institute | Scottsdale | Arizona |
| United States | Virginia G. Piper Cancer Center Pharmacy | Scottsdale | Arizona |
| United States | Fred Hutchinson Cancer Center | Seattle | Washington |
| United States | Seattle Cancer Care Alliance | Seattle | Washington |
| United States | University of Washington Medical Center | Seattle | Washington |
| United States | Highlands Oncology | Springdale | Arkansas |
| United States | Highlands Oncology Group | Springdale | Arkansas |
| United States | Northwest Medical Specialties, PLLC | Tacoma | Washington |
| United States | The Oncology Institute of Hope and Innovation | Whittier | California |
| Lead Sponsor | Collaborator |
|---|---|
| Pfizer |
United States, Bulgaria, Canada, Japan, Russian Federation, Ukraine,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of patients with dose limiting toxicities in the Dose Escalation portion | up to 28 days | ||
| Primary | 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 | |
| Primary | 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 | |
| Primary | 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 | |
| Primary | 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 | |
| Primary | 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 | |
| Primary | 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 | |
| Primary | 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 | 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 | |
| Secondary | 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) | ||
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | Tumor Response observed in patients in Dose Escalation and Dose Finding portion | baseline up to approximately 24 months | ||
| Secondary | 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 | ||
| Secondary | 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 | ||
| Secondary | 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 | ||
| Secondary | Overall Survival observed in patients enrolled in the Dose Expansion Arms | baseline up to approximately 24 months | ||
| Secondary | 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 |