Safety Study of Enzalutamide (MDV3100) in Patients With Incurable Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT01597193
- Lead Sponsor
- Pfizer
- Brief Summary
The purpose of this study is to determine the safety, tolerability and pharmacokinetics of enzalutamide alone and in combination with anastrozole, or exemestane, or fulvestrant in patients with incurable breast cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 101
- Histologically confirmed breast cancer with accompanying pathology report;
- Submit unstained representative tumor specimen, either as a paraffin block (preferred) or ≥ 10 unstained slides
- Received at least 2 lines of systemic therapy in the advanced setting (for enzalutamide alone arm only);
- Eastern Cooperative Oncology Group performance (ECOG) status of 0 or 1;
- Estimated life expectancy of at least 3 months
- Severe concurrent disease, infection, or comorbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment;
- Pregnant or lactating;
- Known or suspected brain metastasis or leptomeningeal disease;
- History of another malignancy within the previous 5 years other than curatively treated in situ carcinomas;
- For patients who are enrolled to receive enzalutamide plus anastrozole or exemestane or fulvestrant must not have received tamoxifen or any medication known to be a potent CYP3A4 inducer or inhibitor.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description enzalutamide (80-mg with increase to 160 mg) enzalutamide enzalutamide be provided as two or four 40-mg capsules by mouth daily enzalutamide and anastrozole anastrozole enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with anastrozole (1 mg) administered as one 1-mg tablet by mouth once daily. enzalutamide and anastrozole enzalutamide enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with anastrozole (1 mg) administered as one 1-mg tablet by mouth once daily. enzalutamide and exemestane 25 mg exemestane enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with exemestane administered as one 25-mg tablet daily enzalutamide and exemestane 50 mg enzalutamide enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with exemestane administered as two 25-mg tablets daily enzalutamide and fulvestrant fulvestrant enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with fulvestrant (500 mg) administered as two 250-mg intramuscular injections every 28 days enzalutamide and exemestane 25 mg enzalutamide enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with exemestane administered as one 25-mg tablet daily enzalutamide and exemestane 50 mg exemestane enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with exemestane administered as two 25-mg tablets daily enzalutamide and fulvestrant enzalutamide enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with fulvestrant (500 mg) administered as two 250-mg intramuscular injections every 28 days
- Primary Outcome Measures
Name Time Method Dose-Escalation Phase: Percentage of Participants With Dose-limiting Toxicity (DLTs) Baseline up to Day 35 DLTs were defined as any of following events related to the study drug: Any adverse event (AE) consistent with a seizure of any grade; Grade greater than equal to (\>=) 3 fatigue, diarrhea, nausea, or vomiting that did not improve to Grade 1 within 14 days of initiating standard of care therapy; any Grade \>=3 hematologic toxicity with the following modifications: 1) Grade \>=3 platelet count associated with bleeding, 2) Grade \>=3 absolute neutrophil count that persists for 7 or more days or that was associated with fevers (febrile neutropenia); Grade \>=3 any other non-hematological toxicity that was determined to be related to study drug.
Percentage of Participants With Adverse Events of Grade 3 or Higher Severity by National Cancer Institute Common Toxicity Criteria For Adverse Events (NCI CTCAE) (Version 4.03) Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years) An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity grading based on NCI CTCAE Version 4.03 and defined as Grade 3 AEs = severe or medically significant events but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self-care activities of daily living; Grade 4 AEs = life-threatening, urgent intervention indicated; Grade 5 AEs = death related to adverse event.
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years) An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. SAE was an AE 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 or incapacity, congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose of study drug that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events.
Percentage of Participants Who Discontinued the Study Drug Due to Adverse Events or Serious Adverse Events Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years) An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. SAE was an AE 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 or incapacity, congenital anomaly.
Percentage of Participants Who Require Dose Reductions Due to Adverse Events Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years) An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. SAE was an AE 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 or incapacity, congenital anomaly.
Percentage of Participants With Potentially Clinically Significant Change From Baseline in Vital Signs Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years) Absolute systolic blood pressure (SBP) greater than (\>) 180 millimeter of mercury (mm Hg) and an increase of \>40 mm Hg from baseline; absolute SBP less than (\<) 90 mm Hg and an decrease of \>30 mm Hg from baseline. Absolute diastolic blood pressure (DBP) \>105 mm Hg and an increase of \>30 mm Hg from baseline; absolute DBP \<50 mm Hg and an increase of \>20 mm Hg from baseline. Absolute heart rate \>120 beats per minute (bpm) and an increase of \>30 bpm from baseline; absolute heart rate \<50 bpm and decrease of \>20 bpm from baseline. Participants with any of these abnormalities were reported for this outcome in each arm.
Dose-Escalation Phase: Maximum Plasma Concentration (Cmax) of Enzalutamide and Its Metabolites After Single Dose pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1 Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.
Dose-Escalation Phase: Time to Reach Maximum Plasma Concentration (Tmax) of Enzalutamide and Its Metabolites After Single Dosing pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1 Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.
Dose-Escalation Phase: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of Enzalutamide and Its Metabolites After Single Dose pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post dose on Day 1 Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.
Dose-Escalation Phase: Area Under the Plasma Concentration-time Curve From Time Zero to 72 Hours (AUC72h) of Enzalutamide After Single Dosing pre-dose, 0.5, 1, 2, 4, 6, 24, 48 and 72 hours post dose on Day 1 Dose-Escalation Phase: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Enzalutamide After Single Dosing pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1 AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf).
Dose-Escalation Phase: Terminal Elimination Half-Life (t1/2) of Enzalutamide After Single Dosing pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1 Terminal elimination half-life is the time measured for the plasma concentration of Enzalutamide to decrease by one-half of its initial concentration.
Dose Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Single Dosing pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1 Apparent oral clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Dose Escalation Phase: Apparent Volume of Distribution (Vz/F) of Enzalutamide After Single Dosing pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1 Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Dose-Escalation Phase: Maximum Plasma Concentration (Cmax) of Enzalutamide and Its Metabolites After Multiple Dosing pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50 Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.
Dose-Escalation Phase: Time to Reach Maximum Plasma Concentration (Tmax) of Enzalutamide and Its Metabolites After Multiple Dosing pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50 Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.
Dose-Escalation Phase: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Enzalutamide and Its Metabolites After Multiple Dosing pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50 Area under the plasma concentration versus time-curve from time zero to end of dosing interval (AUCtau), where dosing interval was 24 hours. Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.
Dose-Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Multiple Dosing pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50 Apparent oral clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Dose-Escalation Phase: Peak-to-Trough Ratio of Enzalutamide and Its Metabolites After Multiple Dosing pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50 Peak-to-trough ratio was calculated by dividing Cmax with Cmin of Enzalutamide and its Metabolites. Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide. Cmax was maximum plasma concentration during the dosing interval and Cmin was minimum observed plasma concentration during the dosing interval.
Dose-Escalation Phase: Accumulation Ratio of AUC24 of Enzalutamide and Its Metabolites After Multiple Dosing pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 1 and 50 Accumulation Ratio was defined as the ratio of AUC24 of Day 50 to AUC24 of Day 1, where AUC24 was area under the plasma concentration-time curve from time zero to 24 hours post-dose. Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.
- Secondary Outcome Measures
Name Time Method Dose-Expansion Phase: Trough Plasma Concentration for Enzalutamide pre-dose on Day 57
Trial Locations
- Locations (13)
Florida Cancer Specialists
🇺🇸Sarasota, Florida, United States
Tennessee Oncology, PLLC.
🇺🇸Nashville, Tennessee, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
ATTN-Research Pharmacist
🇺🇸Aurora, Colorado, United States
Connecticut Multispecialty Group
🇺🇸Enfield, Connecticut, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital, Anschutz Outpatient Pavilion
🇺🇸Aurora, Colorado, United States
The West Clinic, PC
🇺🇸Corinth, Mississippi, United States
Memorial Sloan Kettering Cancer Center - IDS Pharmacy
🇺🇸New York, New York, United States
The West Clinic
🇺🇸Memphis, Tennessee, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center - OPD Pharmacy
🇺🇸New York, New York, United States
The Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States