CompletedNCT01597193Updated May 8, 2019Results posted

Safety Study of Enzalutamide (MDV3100) in Patients With Incurable Breast Cancer

A Phase 1 interventional study of enzalutamide and anastrozole in Breast Cancer, sponsored by Pfizer. Completed at 17 sites in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-05-08.

Sponsored by Pfizer · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 101
Allocation: Non-randomized
Ages: 18 Years and older
Sex: Female

Study 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.

Conditions studied

Breast Cancer

Browse trials for

Breast Neoplasms 12,544

Keywords

enzalutamide
MDV3100
breast cancer

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 101 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.

Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: Female
Accepts healthy volunteers: No

Inclusion criteria

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

Exclusion criteria

Exclusion Criteria:

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

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Masking: None (open label)
Enrollment: 101 participants (actual)

Study arms

Experimental
enzalutamide (80-mg with increase to 160 mg)
enzalutamide be provided as two or four 40-mg capsules by mouth daily
Drug: enzalutamide
Experimental
enzalutamide and 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.
Drug: anastrozole · Drug: enzalutamide
Experimental
enzalutamide and exemestane 25 mg
enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with exemestane administered as one 25-mg tablet daily
Drug: exemestane · Drug: enzalutamide
Experimental
enzalutamide and exemestane 50 mg
enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with exemestane administered as two 25-mg tablets daily
Drug: enzalutamide · Drug: exemestane
Experimental
enzalutamide and 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
Drug: fulvestrant · Drug: enzalutamide

Interventions

Drugenzalutamide
80 mg (2 capsules) or 160 mg (4 capsules) taken orally daily.
Also known as: MDV3100, Xtandi
Druganastrozole
1 mg/day
Also known as: Arimidex
Drugexemestane
The exemestane dose is 25mg daily.
Also known as: Aromasin
Drugfulvestrant
500 mg every 28 days
Also known as: Faslodex
Drugenzalutamide
160 mg (4 capsules) taken orally daily.
Also known as: MDV3100, Xtandi
Drugexemestane
The exemestane dose is 50 mg daily.
Also known as: Aromasin

What researchers measure

Primary outcomes

Dose-Escalation Phase: Percentage of Participants With Dose-limiting Toxicity (DLTs)
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.
Time frame: Baseline up to Day 35
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)
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.
Time frame: 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)
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
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.
Time frame: 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)
Percentage of Participants Who Discontinued the Study Drug Due to Adverse Events or Serious Adverse Events
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.
Time frame: 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)
Percentage of Participants Who Require Dose Reductions Due to Adverse Events
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.
Time frame: 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)
Percentage of Participants With Potentially Clinically Significant Change From Baseline in Vital Signs
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.
Time frame: 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)
Dose-Escalation Phase: Maximum Plasma Concentration (Cmax) of Enzalutamide and Its Metabolites After Single Dose
Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1
Dose-Escalation Phase: Time to Reach Maximum Plasma Concentration (Tmax) of Enzalutamide and Its Metabolites After Single Dosing
Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1
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
Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.
Time frame: pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post dose on Day 1
Dose-Escalation Phase: Area Under the Plasma Concentration-time Curve From Time Zero to 72 Hours (AUC72h) of Enzalutamide After Single Dosing
Time frame: 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
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf).
Time frame: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1
Dose-Escalation Phase: Terminal Elimination Half-Life (t1/2) of Enzalutamide After Single Dosing
Terminal elimination half-life is the time measured for the plasma concentration of Enzalutamide to decrease by one-half of its initial concentration.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1
Dose Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Single Dosing
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.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1
Dose Escalation Phase: Apparent Volume of Distribution (Vz/F) of Enzalutamide After Single Dosing
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.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1
Dose-Escalation Phase: Maximum Plasma Concentration (Cmax) of Enzalutamide and Its Metabolites After Multiple Dosing
Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50
Dose-Escalation Phase: Time to Reach Maximum Plasma Concentration (Tmax) of Enzalutamide and Its Metabolites After Multiple Dosing
Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50
Dose-Escalation Phase: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Enzalutamide and Its Metabolites After Multiple Dosing
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.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50
Dose-Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Multiple Dosing
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.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50
Dose-Escalation Phase: Peak-to-Trough Ratio of Enzalutamide and Its Metabolites After Multiple Dosing
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.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50
Dose-Escalation Phase: Accumulation Ratio of AUC24 of Enzalutamide and Its Metabolites After Multiple Dosing
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.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 1 and 50

Secondary outcomes

Dose-Expansion Phase: Trough Plasma Concentration for Enzalutamide
Time frame: pre-dose on Day 57

Results

Posted May 8, 2019

Limitations and caveats

Prioritization of outcome measures as primary and secondary was based on the study team's discretion.

Participant flow

Stage 1: Dose Escalation (141 Days)

Participant flow — Stage 1: Dose Escalation (141 Days)
Milestone	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg
Started	7	8
Completed	0	0
Not completed	7	8
Withdrew: Disease progression	7	8

Stage 2: Dose Expansion (1067 Days)

Participant flow — Stage 2: Dose Expansion (1067 Days)
Milestone	Dose Expansion: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg	Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
Started	14	20	16	23	11
Completed	0	0	0	0	0
Not completed	14	20	16	23	11
Withdrew: Adverse event	0	1	2	3	0
Withdrew: Disease progression	14	18	14	18	11
Withdrew: Other	0	0	0	1	0
Withdrew: Withdrawal by subject	0	1	0	1	0

Outcome measures

PrimaryDose-Escalation Phase: Percentage of Participants With Dose-limiting Toxicity (DLTs)

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.

Time frame:: Baseline up to Day 35
Reported as:: Number · percentage of participants

Dose-Escalation Phase: Percentage of Participants With Dose-limiting Toxicity (DLTs)
percentage of participants	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg
Dose-Escalation Phase: Percentage of Participants With Dose-limiting Toxicity (DLTs)	16.7	0.0

PrimaryPercentage 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)

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.

Time frame:: 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)
Reported as:: Number · percentage of participants

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)
percentage of participants	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg	Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
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)	57.1	12.5	21.4	30.0	37.5	39.1	36.4

PrimaryPercentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)

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.

Time frame:: 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)
Reported as:: Number · percentage of participants

Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
percentage of participants	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg	Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)	28.6	12.5	14.3	5.0	31.3	13.0	18.2

PrimaryPercentage of Participants Who Discontinued the Study Drug Due to Adverse Events or Serious Adverse Events

Time frame:: 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)
Reported as:: Number · percentage of participants

Percentage of Participants Who Discontinued the Study Drug Due to Adverse Events or Serious Adverse Events
percentage of participants	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg	Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
Percentage of Participants Who Discontinued the Study Drug Due to Adverse Events or Serious Adverse Events	0.0	0.0	7.1	5.0	12.5	13.0	0.0

PrimaryPercentage of Participants Who Require Dose Reductions Due to Adverse Events

Time frame:: 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)
Reported as:: Number · percentage of participants

Percentage of Participants Who Require Dose Reductions Due to Adverse Events
percentage of participants	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg	Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
Percentage of Participants Who Require Dose Reductions Due to Adverse Events	0.0	0.0	0.0	20.0	12.5	8.7	18.2

PrimaryPercentage of Participants With Potentially Clinically Significant Change From Baseline in Vital Signs

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.

Time frame:: 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)
Reported as:: Number · percentage of participants

Percentage of Participants With Potentially Clinically Significant Change From Baseline in Vital Signs
percentage of participants	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg	Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
Blood pressure	1	0	1	0	1	2	1
Heart rate	0	2	1	0	0	0	0

PrimaryDose-Escalation Phase: Maximum Plasma Concentration (Cmax) of Enzalutamide and Its Metabolites After Single Dose

Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.

Time frame:: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1
Reported as:: Mean · micrograms per milliliter

Dose-Escalation Phase: Maximum Plasma Concentration (Cmax) of Enzalutamide and Its Metabolites After Single Dose
micrograms per milliliter	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg
Enzalutamide	1.90 ± 0.757	4.01 ± 2.09
M1	0.0375 ± 0.0286	0.0707 ± 0.0379
M2	0.0879 ± 0.0718	0.184 ± 0.0689

PrimaryDose-Escalation Phase: Time to Reach Maximum Plasma Concentration (Tmax) of Enzalutamide and Its Metabolites After Single Dosing

Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.

Time frame:: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1
Reported as:: Median · hours

Dose-Escalation Phase: Time to Reach Maximum Plasma Concentration (Tmax) of Enzalutamide and Its Metabolites After Single Dosing
hours	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg
Enzalutamide	0.500 (0.500 to 2.00)	1.00 (0.350 to 4.00)
M1	24.1 (5.55 to 25.1)	23.1 (4.00 to 23.9)
M2	23.9 (21.1 to 25.1)	23.7 (20.8 to 24.5)

PrimaryDose-Escalation Phase: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of Enzalutamide and Its Metabolites After Single Dose

Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.

Time frame:: pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post dose on Day 1
Reported as:: Mean · micrograms*hour per milliliter

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
micrograms*hour per milliliter	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg
Enzalutamide	17.3 ± 8.32	41.6 ± 8.19
M1	0.632 ± 0.385	1.20 ± 0.648
M2	1.13 ± 0.916	2.76 ± 1.00

PrimaryDose-Escalation Phase: Area Under the Plasma Concentration-time Curve From Time Zero to 72 Hours (AUC72h) of Enzalutamide After Single Dosing

Time frame:: pre-dose, 0.5, 1, 2, 4, 6, 24, 48 and 72 hours post dose on Day 1
Reported as:: Mean · micrograms*hour per milliliter

Dose-Escalation Phase: Area Under the Plasma Concentration-time Curve From Time Zero to 72 Hours (AUC72h) of Enzalutamide After Single Dosing
micrograms*hour per milliliter	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg
Dose-Escalation Phase: Area Under the Plasma Concentration-time Curve From Time Zero to 72 Hours (AUC72h) of Enzalutamide After Single Dosing	43.0 ± 21.4	107 ± 15.6

PrimaryDose-Escalation Phase: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Enzalutamide After Single Dosing

AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf).

Time frame:: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1
Reported as:: Mean · micrograms*hour per milliliter

Dose-Escalation Phase: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Enzalutamide After Single Dosing
micrograms*hour per milliliter	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg
Dose-Escalation Phase: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Enzalutamide After Single Dosing	208 ± 66.0	478 ± 232

PrimaryDose-Escalation Phase: Terminal Elimination Half-Life (t1/2) of Enzalutamide After Single Dosing

Terminal elimination half-life is the time measured for the plasma concentration of Enzalutamide to decrease by one-half of its initial concentration.

Time frame:: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1
Reported as:: Mean · hours

Dose-Escalation Phase: Terminal Elimination Half-Life (t1/2) of Enzalutamide After Single Dosing
hours	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg
Dose-Escalation Phase: Terminal Elimination Half-Life (t1/2) of Enzalutamide After Single Dosing	280 ± 170	198 ± 105

PrimaryDose Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Single Dosing

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.

Time frame:: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1
Reported as:: Mean · liter per hour

Dose Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Single Dosing
liter per hour	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg
Dose Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Single Dosing	0.426 ± 0.160	0.382 ± 0.115

PrimaryDose Escalation Phase: Apparent Volume of Distribution (Vz/F) of Enzalutamide After Single Dosing

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.

Time frame:: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1
Reported as:: Mean · liter

Dose Escalation Phase: Apparent Volume of Distribution (Vz/F) of Enzalutamide After Single Dosing
liter	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg
Dose Escalation Phase: Apparent Volume of Distribution (Vz/F) of Enzalutamide After Single Dosing	151 ± 73.6	94.5 ± 13.7

PrimaryDose-Escalation Phase: Maximum Plasma Concentration (Cmax) of Enzalutamide and Its Metabolites After Multiple Dosing

Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.

Time frame:: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50
Reported as:: Mean · micrograms per milliliter

Dose-Escalation Phase: Maximum Plasma Concentration (Cmax) of Enzalutamide and Its Metabolites After Multiple Dosing
micrograms per milliliter	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg
Enzalutamide	11.6 ± 1.95	15.3 ± 2.62
M1	1.77 ± 0.521	6.24 ± 2.28
M2	6.42 ± 0.132	14.1 ± 3.66

PrimaryDose-Escalation Phase: Time to Reach Maximum Plasma Concentration (Tmax) of Enzalutamide and Its Metabolites After Multiple Dosing

Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.

Time frame:: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50
Reported as:: Median · hours

Dose-Escalation Phase: Time to Reach Maximum Plasma Concentration (Tmax) of Enzalutamide and Its Metabolites After Multiple Dosing
hours	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg
Enzalutamide	0.500 (0.00 to 5.50)	1.00 (0.570 to 4.00)
M1	5.70 (0.500 to 24.0)	2.29 (0.00 to 24.0)
M2	24.0 (0.570 to 24.0)	0.58 (0.00 to 24.0)

PrimaryDose-Escalation Phase: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Enzalutamide and Its Metabolites After Multiple Dosing

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.

Time frame:: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50
Reported as:: Mean · milligram*hour per milliliter

Dose-Escalation Phase: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Enzalutamide and Its Metabolites After Multiple Dosing
milligram*hour per milliliter	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg
Enzalutamide	207 ± 24.3	325 ± 61.6
M1	33.0 ± 13.0	120 ± 56.0
M2	140 ± 6.08	317 ± 89.4

PrimaryDose-Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Multiple Dosing

Time frame:: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50
Reported as:: Mean · liter per hour

Dose-Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Multiple Dosing
liter per hour	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg
Dose-Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Multiple Dosing	0.390 ± 0.0491	0.507 ± 0.0906

PrimaryDose-Escalation Phase: Peak-to-Trough Ratio of Enzalutamide and Its Metabolites After Multiple Dosing

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.

Time frame:: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50
Reported as:: Mean · ratio

Dose-Escalation Phase: Peak-to-Trough Ratio of Enzalutamide and Its Metabolites After Multiple Dosing
ratio	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg
Enzalutamide	1.39 ± 0.400	1.14 ± 0.174
M1	1.32 ± 0.407	1.42 ± 0.388
M2	0.999 ± 0.0012	1.00 ± 0.0420

PrimaryDose-Escalation Phase: Accumulation Ratio of AUC24 of Enzalutamide and Its Metabolites After Multiple Dosing

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.

Time frame:: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 1 and 50
Reported as:: Mean · ratio

Dose-Escalation Phase: Accumulation Ratio of AUC24 of Enzalutamide and Its Metabolites After Multiple Dosing
ratio	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg
Enzalutamide	17.9 ± 2.69	9.39 ± 3.75
M1	47.6 ± 21.4	68.0 ± 35.8
M2	157 ± 48.2	77.8 ± 35.7

SecondaryDose-Expansion Phase: Trough Plasma Concentration for Enzalutamide

Time frame:: pre-dose on Day 57
Reported as:: Mean · micrograms per milliliter

Dose-Expansion Phase: Trough Plasma Concentration for Enzalutamide
micrograms per milliliter	Dose Expansion: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg	Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
Dose-Expansion Phase: Trough Plasma Concentration for Enzalutamide	13.40 ± 2.51	14.33 ± 3.99	13.52 ± 2.62	12.41 ± 3.76	11.62 ± 4.69

Adverse events

Collected over 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). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Dose Escalation: Enzalutamide 80 mg	0/7 (0%)	2/7 (28.6%)	7/7 (100%)
Dose Escalation: Enzalutamide 160 mg	0/8 (0%)	1/8 (12.5%)	8/8 (100%)
Dose Expansion: Enzalutamide 160 mg	1/14 (7.1%)	2/14 (14.3%)	14/14 (100%)
Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg	0/20 (0%)	1/20 (5%)	20/20 (100%)
Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg	0/16 (0%)	5/16 (31.3%)	15/16 (93.8%)
Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg	0/23 (0%)	3/23 (13%)	21/23 (91.3%)
Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg	0/11 (0%)	2/11 (18.2%)	11/11 (100%)

Most frequent serious events

Showing 10 of 21

Most frequent serious events
Event	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg	Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
Adrenal InsufficiencyEndocrine disorders	1/7	0/8	0/14	0/20	0/16	0/23	0/11
HydronephrosisRenal and urinary disorders	1/7	0/8	0/14	0/20	0/16	0/23	0/11
AnaemiaBlood and lymphatic system disorders	0/7	1/8	0/14	0/20	0/16	0/23	0/11
Iron Deficiency AnaemiaBlood and lymphatic system disorders	0/7	0/8	0/14	0/20	0/16	0/23	1/11
Gastritis ErosiveGastrointestinal disorders	0/7	0/8	0/14	0/20	0/16	0/23	1/11
Urinary Tract InfectionInfections and infestations	0/7	0/8	0/14	0/20	0/16	0/23	1/11
DehydrationMetabolism and nutrition disorders	0/7	0/8	0/14	0/20	0/16	0/23	1/11
PneumoniaInfections and infestations	0/7	0/8	0/14	0/20	0/16	2/23	0/11
Abdominal PainGastrointestinal disorders	0/7	0/8	1/14	0/20	0/16	0/23	0/11
UrosepsisInfections and infestations	0/7	0/8	1/14	0/20	0/16	0/23	0/11

Most frequent other events

Showing 10 of 182

Most frequent other events
Event	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg	Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
FatigueGeneral disorders	0/7	2/8	8/14	12/20	8/16	12/23	8/11
NauseaGastrointestinal disorders	1/7	3/8	8/14	9/20	7/16	12/23	8/11
Aspartate Aminotransferase IncreasedInvestigations	4/7	1/8	0/14	2/20	1/16	0/23	0/11
Back PainMusculoskeletal and connective tissue disorders	0/7	1/8	5/14	3/20	2/16	5/23	6/11
HypertensionVascular disorders	1/7	4/8	1/14	1/20	0/16	5/23	2/11
Decreased AppetiteMetabolism and nutrition disorders	1/7	1/8	1/14	10/20	5/16	4/23	2/11
CoughRespiratory, thoracic and mediastinal disorders	0/7	4/8	2/14	3/20	3/16	4/23	1/11
DiarrhoeaGastrointestinal disorders	3/7	1/8	2/14	6/20	4/16	3/23	4/11
HyperglycaemiaMetabolism and nutrition disorders	1/7	3/8	0/14	1/20	3/16	2/23	1/11
Nasal CongestionRespiratory, thoracic and mediastinal disorders	0/7	3/8	0/14	0/20	0/16	0/23	0/11

Baseline characteristics

Safety analysis population included all enrolled participants who received at least 1 dose of Enzalutamide.

Age, Customized
Age, Customized(Participants)	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg	Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg	Total
Less than (<) 65 years	6	5	11	12	13	10	6	63
Between 65 to 74 years	1	3	2	5	2	12	4	29
Greater than or equal to (>=) 75 years	0	0	1	3	1	1	1	7

Sex: Female, Male
Sex: Female, Male(Participants)	Dose Escalation: Enzalutamide 80 mg	Dose Escalation: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg	Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg	Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg	Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg	Total
Female	7	8	14	20	16	23	11	99
Male	0	0	0	0	0	0	0	0

Study locations

17 sites

ATTN-Research Pharmacist
Aurora, Colorado 80045, United States
University of Colorado Cancer Center
Aurora, Colorado 80045, United States
University of Colorado Hospital, Anschutz Outpatient Pavilion
Aurora, Colorado 80045, United States
Connecticut Multispecialty Group
Enfield, Connecticut 06082, United States
Florida Cancer Specialists
Sarasota, Florida 34232, United States
Karmanos Cancer Institute
Detroit, Michigan 48201, United States
The West Clinic, PC
Corinth, Mississippi 38834, United States
The West Clinic
Southaven, Mississippi 38671, United States
Memorial Sloan Kettering Cancer Center
New York, New York 10022, United States
Memorial Sloan Kettering Cancer Center - IDS Pharmacy
New York, New York 10065, United States
Memorial Sloan Kettering Cancer Center - OPD Pharmacy
New York, New York 10065, United States
Memorial Sloan Kettering Cancer Center
New York, New York 10065, United States
The West Clinic
Germantown, Tennessee 38138, United States
The West Clinic
Memphis, Tennessee 38104, United States
The West Clinic
Memphis, Tennessee 38120, United States
Tennessee Oncology, PLLC.
Nashville, Tennessee 37203, United States
The Sarah Cannon Research Institute
Nashville, Tennessee 37203, United States

References and documents

Individual participant data

Plan to share: No — 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.

No publications or documents are linked to this record.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on May 8, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01597193
Lead sponsor: Pfizer
Collaborators: Astellas Pharma Inc, Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Responsible party: Sponsor
First posted: May 11, 2012
Start date: Apr 30, 2012
Primary completion: Dec 15, 2015
Completion: Jan 22, 2018
Results posted: May 8, 2019
Last update: May 8, 2019

Study contacts

Pfizer Pfizer CT.gov Call Center

study director · Pfizer

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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