Advanced, Androgen Receptor Positive Triple Negative Breast Cancer Clinical Trial
Official title:
A PHASE 2, SINGLE-ARM, OPEN-LABEL, MULTICENTER STUDY OF THE CLINICAL ACTIVITY AND SAFETY OF ENZALUTAMIDE IN PATIENTS WITH ADVANCED, ANDROGEN RECEPTOR-POSITIVE, TRIPLE-NEGATIVE BREAST CANCER
| Verified date | February 2024 |
| Source | Pfizer |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The purpose of this study is to determine if enzalutamide is safe and effective in the treatment of patients with advanced breast cancer that express the androgen receptor but do not express the estrogen or progesterone receptor and are not Her2 amplified.
| Status | Completed |
| Enrollment | 118 |
| Est. completion date | January 10, 2024 |
| Est. primary completion date | March 1, 2015 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Women at least 18 years of age; - Advanced AR+ TNBC; - Availability of a representative tumor specimen: - Either measurable disease or bone only nonmeasurable disease; - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Exclusion Criteria: - Any severe concurrent disease, infection, or comorbid condition; - Any condition or reason that interferes with the patient's ability to participate in the trial, that may cause undue risk, or complicates the interpretation of safety data; - Current or previously treated brain metastasis or active leptomeningeal disease; - Current hormone replacement therapy; - Local palliative radiation therapy within 7 days before day 1; - History of another invasive cancer within 5 years of day 1; - Absolute neutrophil count < 1500/µL, platelet count < 75,000/µL, or hemoglobin < 9 g/dL (5.6 mmol/L) at the screening visit; - Creatinine > 1.5 times upper limit of normal (ULN) at the screening visit; - History of seizure or any condition that may predispose to seizure; - Clinically significant cardiovascular disease; - Active gastrointestinal disorder affecting absorption; - Major surgery within 4 weeks before day 1; - Treatment with any commercially available anticancer agent within 14 days before day 1; - Treatment with any investigational agent within 2 weeks before day 1; - Treatment with any of the following medications within 2 weeks before day 1: Estrogens, including hormone replacement therapy; Androgens (testosterone, dihydroepiandrosterone, etc);Systemic radionuclides (eg, samarium or strontium);Vaccine therapy; - Hypoglycemic episode requiring medical intervention while on insulin treatment within 12 months before day 1; - Hypersensitivity reaction to the active pharmaceutical ingredient or any of the capsule components, including Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene. |
| Country | Name | City | State |
|---|---|---|---|
| Belgium | Institut Jules Bordet | Brussels | |
| Canada | McGill University Health Centre-Cedars Cancer Centre | Montreal | Quebec |
| Canada | Sunnybrook Research Institute | Toronto | Ontario |
| Canada | British Columbia Cancer Agency - Vancouver Centre | Vancouver | British Columbia |
| Ireland | 3rd Floor,Oncology Link office | Dublin | |
| Ireland | Department of Radiology | Dublin | |
| Ireland | Institute for Cancer Research | Dublin | |
| Ireland | Mater Private Hospital | Dublin | |
| Ireland | Pharmacy Department | Dublin | |
| Ireland | Radiology Department | Dublin | |
| Ireland | Pharmacy Department | Dublin 4 | |
| Italy | U.O Farmaceutica, Nuovo Ospedale di Prato Palazzina dei servizi | Prato | |
| Spain | Grupo Hospitalario Quiron - Hospital Quiron Barcelona | Barcelona | |
| Spain | Hospital Universitari Vall d'Hebron | Barcelona | |
| Spain | Hospital Universitario HM Monteprincipe | Boadilla del Monte | Madrid |
| Spain | Centro Intergral Oncologico Clara Campal | Madrid | |
| Spain | Hospital de Madrid Norte-Sanchinarro. | Madrid | |
| Spain | Hospital Universitario 12 Octubre | Madrid | |
| Spain | Hospital Universitario Ramon Y Cajal | Madrid | |
| United Kingdom | Clinical Investigation and Research Unit | Brighton | England |
| United Kingdom | Pharmacy Department | Brighton | England |
| United Kingdom | Radiation Safety Service, Medical Physics Department | Brighton | England |
| United Kingdom | Histopathology Department | Nottingham | England |
| United Kingdom | Nottingham University Hospital | Nottingham | England |
| United Kingdom | Pharmacy Department | Nottingham | England |
| United Kingdom | Radiology Department | Nottingham | England |
| United Kingdom | Department of Radiology | Truro | England |
| United Kingdom | Pharmacy Department | Truro | England |
| United Kingdom | Royal Cornwall Hospitals NHS trust | Truro, Cornwall | England |
| United States | Florida Cancer Specialists | Altamonte Springs | Florida |
| United States | Florida Cancer Specialists | Bonita Springs | Florida |
| United States | Beth Israel Deaconess Medical Center | Boston | Massachusetts |
| United States | Dana-Farber Cancer Institute | Boston | Massachusetts |
| United States | Florida Cancer Specialists | Bradenton | Florida |
| United States | Florida Cancer Specialists | Brandon | Florida |
| United States | Florida Cancer Specialists | Cape Coral | Florida |
| United States | Northwestern Medical Faculty Foundation | Chicago | Illinois |
| United States | Northwestern Medical Faculty Foundation(NMFF)/ Women's Cancer Center Shared Laboratories | Chicago | Illinois |
| United States | Northwestern Memorial Hospital | Chicago | Illinois |
| United States | The University of Chicago | Chicago | Illinois |
| United States | The University of Chicago Medical Center, Investigational Drug Service Department of Pharmacy | Chicago | Illinois |
| United States | Oncology Hematology Care, Inc. | Cincinnati | Ohio |
| United States | Oncology Hematology Care, Inc. | Cincinnati | Ohio |
| United States | Oncology Hematology Care, Inc. | Cincinnati | Ohio |
| United States | Oncology Hematology Care, Inc. | Cincinnati | Ohio |
| United States | Oncology Hematology Care, Inc. | Cincinnati | Ohio |
| United States | Florida Cancer Specialists | Clearwater | Florida |
| United States | Rocky Mountain Cancer Centers | Colorado Springs | Colorado |
| United States | The West Clinic, PC | Corinth | Mississippi |
| United States | Oncology Hematology Care, Inc. | Crestview Hills | Kentucky |
| United States | Texas Oncology-Baylor Charles A. Sammons Cancer Center | Dallas | Texas |
| United States | Tennessee Oncology, PLLC | Dickson | Tennessee |
| United States | Oncology Hematology Care, Inc. | Fairfield | Ohio |
| United States | Florida Cancer Specialists | Fort Myers | Florida |
| United States | Florida Cancer Specialists | Fort Myers | Florida |
| United States | Florida Cancer Specialists | Fort Myers | Florida |
| United States | Tennessee Oncology, PLLC | Franklin | Tennessee |
| United States | Florida Cancer Specialists | Gainesville | Florida |
| United States | Tennessee Oncology, PLLC | Gallatin | Tennessee |
| United States | Cone Health Cancer Center | Greensboro | North Carolina |
| United States | Wesley Long Community Hospital | Greensboro | North Carolina |
| United States | Greenville Health System | Greenville | South Carolina |
| United States | Tennessee Oncology, PLLC | Hermitage | Tennessee |
| United States | Florida Cancer Specialists | Hudson | Florida |
| United States | Indiana University Health Hospital | Indianapolis | Indiana |
| United States | Indiana University Health Melvin and Bren Simon Cancer Center | Indianapolis | Indiana |
| United States | Investigational Drug Services | Indianapolis | Indiana |
| United States | Sidney and Lois Eskenazi Hospital | Indianapolis | Indiana |
| United States | Springmill Medical Clinic | Indianapolis | Indiana |
| United States | Rocky Mountain Cancer Centers | Lakewood | Colorado |
| United States | Florida Cancer Specialists | Largo | Florida |
| United States | Tennessee Oncology, PLLC | Lebanon | Tennessee |
| United States | Rocky Mountain Cancer Centers | Lone Tree | Colorado |
| United States | Texas Oncology - Longview Cancer Center | Longview | Texas |
| United States | Virginia Cancer Institute | Mechanicsville | Virginia |
| United States | The West Clinic, PC | Memphis | Tennessee |
| United States | The West Clinic, PC | Memphis | Tennessee |
| United States | Virginia Cancer Institute | Midlothian | Virginia |
| United States | Hematology Oncology Associates of Northern NJ | Morristown | New Jersey |
| United States | Tennessee Oncology, PLLC | Murfreesboro | Tennessee |
| United States | Florida Cancer Specialists | Naples | Florida |
| United States | Henry-Joyce Cancer Clinic | Nashville | Tennessee |
| United States | Tennessee Oncology, PLLC | Nashville | Tennessee |
| United States | Tennessee Oncology, PLLC | Nashville | Tennessee |
| United States | Tennessee Oncology, PLLC | Nashville | Tennessee |
| United States | Tennessee Oncology, PLLC | Nashville | Tennessee |
| United States | The Sarah Cannon Research Institute | Nashville | Tennessee |
| United States | Vanderbilt Breast Center at One Hundred Oaks | Nashville | Tennessee |
| United States | Vanderbilt Health Pharmacy One Hundred Oaks | Nashville | Tennessee |
| United States | University of Chicago Comprehensive Cancer Center at Silver Cross Hospital | New Lenox | Illinois |
| United States | Florida Cancer Specialists | New Port Richey | Florida |
| United States | Memorial Sloan Kettering - I Chemotherapy Practice/Investigational Drug Service | New York | New York |
| United States | Memorial Sloan-Kettering Cancer Center | New York | New York |
| United States | Virginia Oncology Associates | Newport News | Virginia |
| United States | Virginia Oncology Associates | Norfolk | Virginia |
| United States | Florida Cancer Specialists | Orange City | Florida |
| United States | Florida Cancer Specialists | Orlando | Florida |
| United States | Florida Cancer Specialists | Port Charlotte | Florida |
| United States | Virginia Cancer Institute | Richmond | Virginia |
| United States | Virginia Cancer Institute | Richmond | Virginia |
| United States | Barnes-Jewish Hospital | Saint Louis | Missouri |
| United States | Siteman Cancer Center-South County | Saint Louis | Missouri |
| United States | Siteman Cancer Center-West County | Saint Louis | Missouri |
| United States | Washington University Infusion Center Pharmacy | Saint Louis | Missouri |
| United States | Washington University School of Medicine | Saint Louis | Missouri |
| United States | Siteman Cancer Center | Saint Peters | Missouri |
| United States | Florida Cancer Specialists | Saint Petersburg | Florida |
| United States | Florida Cancer Specialists | Sarasota | Florida |
| United States | Florida Cancer Specialists | Sarasota | Florida |
| United States | Greenville Health System | Seneca | South Carolina |
| United States | Tennessee Oncology, PLLC | Smyrna | Tennessee |
| United States | The West Clinic, PC | Southaven | Mississippi |
| United States | Greenville Health System | Spartanburg | South Carolina |
| United States | Florida Cancer Specialists | Spring Hill | Florida |
| United States | Florida Cancer Specialists | Tampa | Florida |
| United States | Florida Cancer Specialists | Tavares | Florida |
| United States | Texas Oncology-Tyler | Tyler | Texas |
| United States | Florida Cancer Specialists | Venice | Florida |
| United States | Florida Cancer Specialists | Venice | Florida |
| United States | Virginia Oncology Associates | Virginia Beach | Virginia |
| Lead Sponsor | Collaborator |
|---|---|
| Pfizer | Astellas Pharma Inc, Medivation LLC, a wholly owned subsidiary of Pfizer Inc. |
United States, Belgium, Canada, Ireland, Italy, Spain, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Trough Plasma Concentration of Enzalutamide and Its Metabolite, | M2 was the metabolite of enzalutamide. The lower limit of quantitation (LLQ) was 0.0200 micrograms per milliliter (mcg/ml) for enzalutamide and M2. | Predose on Day 1 (Baseline), Week 9 and Week 17 | |
| Other | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AEs was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AEs resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment emergent are events between first dose of study drug and up to 87 weeks that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs. | Baseline up to 87 weeks | |
| Other | Number of Participants With Study Drug Discontinuation Due to Adverse Events | Baseline up to 87 weeks | ||
| Other | Number of Participants With Grade 3 or Higher Adverse Events | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of the AEs was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. As per the NCI CTCAE, version 4.0, Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening and Grade 5= death. Only the participants with treatment-emergent AEs of Grade 3 (severe) or higher grade were reported in this outcome measure. | Baseline up to 87 weeks | |
| Other | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Criteria: Systolic blood pressure (SBP):absolute SBP<90 millimeters of mercury (mmHg) and decrease from baseline (DFB)>30mmHg, absolute SBP>180mmHg and increase from baseline (IFB)>40 mmHg, final visit or 2 consecutive visits SBP>=20 mmHg change from baseline (CFB), most extreme post-baseline SBP>=140mmHg, most extreme post- baseline SBP>=180mmHg, most extreme SBP>=140mmHg and>=20 mmHg CFB, most extreme SBP>=180mmHg and>=20mmHg CFB; diastolic blood pressure (DBP): absolute DBP>105mmHg and IFB>30mmHg, absolute DBP<50mmHg and DFB>20mmHg, final visit or 2 consecutive visits DBP>=15mmHg CFB, most extreme post-baseline DBP>=90mmHg, most extreme post-baseline DBP>=105mmHg, most extreme DBP>=90mmHg and>=15mmHg CFB, most extreme DBP>=105mmHg and>=15mmHg CFB; heart rate<50beats per minute (BPM) and DFB>20BPM or heart rate>120BPM and IFB>30BPM. Only those categories, in which at least 1 subject had data were reported. | Baseline up to 87 weeks | |
| Other | Number of Participants With Change From Baseline in Laboratory Parameters Grades by 2 or More Grades | Laboratory tests included hematology parameters (low lymphocytes, WBC, neutrophils, hemoglobin and platelets) and chemistry parameters (mean albumin, Blood urea nitrogen [BUN], calcium, Lactate dehydrogenase [LDH], alanine aminotransferase, Aspartate aminotransferase , bilirubin, Alkaline phosphatase, creatinine and glucose). Number of participants with change from baseline in laboratory parameters Grades by 2 or More Grades as per National Cancer Institute Common Terminology Criteria (NCI CTC) (Grade 0= within normal limits, Grade 1=Mild, Grade 2=Moderate, Grade 3= Severe, Grade 4= Life-threatening) were reported. | Baseline up to 87 weeks | |
| Primary | Percentage of Participants With Clinical Benefit at Week 16: Evaluable Population | Percentage of participants with a clinical benefit at Week 16 defined as percentage of participants with a best response of complete response (CR), partial response(PR), stable disease(SD) for >= 16 weeks on radiologic imaging based on Investigator assessment using Response Evaluation Criteria in Solid Tumors version 1.1(RECIST 1.1). An estimate of the percentage and its exact 2-sided 85% confidence interval(CI) were calculated using the Blaker method. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in size <10mm short axis. PR: At least 30% decrease in sum of longest diameter (LD) of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. SD: Neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during the study as a reference | Week 16 | |
| Primary | Percentage of Participants With Clinical Benefit at Week 16: Intent-to-Treat (ITT) Population | Percentage of participants with a clinical benefit at Week 16 defined as percentage of participants with a best response of CR, PR, or SD for >= 16 weeks on radiologic imaging based on Investigator assessment using RECIST 1.1. An estimate of the percentage and its exact 2-sided 85% CI were calculated using the Blaker method. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in size <10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. SD: Neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during the study as a reference. | Week 16 | |
| Secondary | Percentage of Participants With Clinical Benefit at Week 24: Evaluable Population | Percentage of participants with a clinical benefit at Week 24 defined as percentage of participants with a best response of CR, PR, or SD for >= 24 weeks on radiologic imaging based on investigator assessment using RECIST 1.1. An estimate of the percentage and its exact 2-sided 85% CI were calculated using the Blaker method. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in size <10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. SD: Neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during the study as a reference. | Week 24 | |
| Secondary | Percentage of Participants With Clinical Benefit at Week 24: ITT Population | Percentage of participants with a clinical benefit at Week 24 defined as percentage of participants with a best response of CR, PR, or SD for >= 24 weeks on radiologic imaging based on investigator assessment using RECIST 1.1. An estimate of the percentage and its exact 2-sided 85% CI were calculated using the Blaker method. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in size <10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. SD: Neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during the study as a reference. | Week 24 | |
| Secondary | Percentage of Participants With Best Objective Response: Evaluable Population | Percentage of participants with best objective response defined as percentage of participants with a best response of CR and PR based on investigator assessment of target, non-target and new lesions using RECIST 1.1. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in <10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. | From Baseline up to disease progression or death due to any cause (up to 87 Weeks) | |
| Secondary | Percentage of Participants With Best Objective Response: ITT Population | Percentage of participants with best objective response defined as percentage of participants with a best response of CR and PR based on investigator assessment of target, non-target and new lesions using RECIST 1.1. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in <10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. | From Baseline up to disease progression or death due to any cause (up to 87 Weeks) | |
| Secondary | Progression-Free Survival (PFS): Evaluable Population | PFS was defined as the time (in weeks) from the date of first dose of study drug to the date of documented disease progression or death due to any cause whichever occurs first as determined by the investigator using RECIST 1.1. As per RECIST 1.1, progression was defined as: >=20 percent increase in sum of LD of target lesions taking as a reference the smallest sum of the LD recorded since the treatment started, or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions. | From Baseline up to disease progression or death due to any cause (up to 87 Weeks) | |
| Secondary | Progression-Free Survival: ITT Population | PFS was defined as the time (in weeks) from the date of first dose of study drug to the date of documented disease progression or death due to any cause whichever occurs first as determined by the investigator using RECIST 1.1. As per RECIST 1.1, progression was defined as: >=20 percent increase in sum of LD of target lesions taking as a reference the smallest sum of the LD recorded since the treatment started, or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions. | From Baseline up to disease progression or death due to any cause (up to 87 Weeks) |