Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Fulvestrant

Exemestane

Anastrozole

Antineoplastic Agents, Hormonal

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Aromatase Inhibitors

Enzyme Inhibitors

enzalutamide be provided as two or four 40-mg capsules by mouth daily

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 (160 mg) administered as four 40-mg capsules by mouth once daily in combination with exemestane administered as one 25-mg tablet daily

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 (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

80 mg (2 capsules) or 160 mg (4 capsules) taken orally daily.

enzalutamide

anastrozole

exemestane

fulvestrant

Pfizer Pfizer CT.gov Call Center

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.

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

A PHASE 1 OPEN-LABEL, DOSE ESCALATION STUDY EVALUATING THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF ENZALUTAMIDE (FORMERLY MDV3100) IN PATIENTS WITH INCURABLE BREAST CANCER

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.

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.

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.

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.

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.

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.

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

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

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

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.

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.

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.

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.

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.

Astellas Pharma Inc

Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

Pfizer

Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.

Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.

Dose Escalation: Enzalutamide 80 mg

Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.

Dose Escalation: Enzalutamide 160 mg

Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.

Dose Expansion: Enzalutamide 160 mg

Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the anastrozole 1 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.

Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg

Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 25 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.

Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg

Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 50 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.

Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg

Participants received enzalutamide 160 mg (four 40 mg) capsule once daily in combination with the fulvestrant 500 mg intramuscular injection, once every 28 days until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.

Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg

Total

Less than (<) 65 years

Between 65 to 74 years

Greater than or equal to (>=) 75 years

Age, Customized

Sex: Female, Male

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

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

Pfizer ClinicalTrials.gov Call Center

Safety analysis population included all enrolled participants who received at least 1 dose of Enzalutamide. Here, number of participants analyzed signifies those participants who were evaluable for this outcome measure.

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

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 With Treatment-Emergent Serious Adverse Events (SAEs)

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

Percentage of Participants Who Require Dose Reductions Due to Adverse Events

Blood pressure

Heart rate

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

Enzalutamide

Pharmacokinetic (PK) analysis population included all participants who had at least 1 dose of Enzalutamide and had sufficient PK data to calculate at least 1 of the PK parameters of interest in at least 1 treatment period.

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

PK analysis population included all participants who had at least 1 dose of Enzalutamide and had sufficient PK data to calculate at least 1 of the PK parameters of interest in at least 1 treatment period.

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

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

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

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

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

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

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

PK analysis population included all participants who had at least 1 dose of Enzalutamide and had sufficient PK data to calculate at least 1 of the PK parameters of interest in at least 1 treatment period. Here, number of participants analyzed signifies those participants who were evaluable for this outcome measure.

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

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

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

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

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

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

Dose-Expansion Phase: Trough Plasma Concentration for Enzalutamide

Participants received enzalutamide 80 milligram (mg) (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.

Spots Global Cancer Trial Database for Safety Study of Enzalutamide (MDV3100) in Patients With Incurable Breast Cancer

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