Breast CancerPhase 1NCT01597193

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

A Phase 1 study testing enzalutamide, anastrozole and exemestane in people with Breast Cancer, run by Pfizer at 17 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Breast Cancer
What is being tested?: enzalutamide, anastrozole and exemestane
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 101 participants
Where: 17 sitesUnited States
Study dates: 30 Apr 2012to 22 Jan 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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.

Trial locations and contacts

17 sites in 1 country.

City, postcode or hospital

17 sites in 1 country

United States17 sites

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

Other trials in United States

About this study

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

Conditions: Breast Cancer
Being tested: enzalutamide, anastrozole, exemestane, fulvestrant
Keywords: enzalutamide, MDV3100, breast cancer
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

enzalutamideDrug
Also called MDV3100, Xtandi
80 mg (2 capsules) or 160 mg (4 capsules) taken orally daily.
anastrozoleDrug
Also called Arimidex
1 mg/day
exemestaneDrug
Also called Aromasin
The exemestane dose is 25mg daily.
fulvestrantDrug
Also called Faslodex
500 mg every 28 days
enzalutamideDrug
Also called MDV3100, Xtandi
160 mg (4 capsules) taken orally daily.
exemestaneDrug
Also called Aromasin
The exemestane dose is 50 mg daily.

Study groups in NCT01597193
Study group	Role	What they receive
enzalutamide (80-mg with increase to 160 mg)	Experimental	enzalutamide be provided as two or four 40-mg capsules by mouth daily Receives: Drug: enzalutamide
enzalutamide and anastrozole	Experimental	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. Receives: Drug: anastrozole; Drug: enzalutamide
enzalutamide and exemestane 25 mg	Experimental	enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with exemestane administered as one 25-mg tablet daily Receives: Drug: exemestane; Drug: enzalutamide
enzalutamide and exemestane 50 mg	Experimental	enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with exemestane administered as two 25-mg tablets daily Receives: Drug: enzalutamide; Drug: exemestane
enzalutamide and fulvestrant	Experimental	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 Receives: Drug: fulvestrant; Drug: enzalutamide

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 1 and 50

Secondary outcomes (1)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Apr 201222 Jan 2018

First posted11 May 2012 (estimated)
Study start30 Apr 2012
Primary completion15 Dec 2015
Study completion22 Jan 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Breast CancerStudies of the same condition, open and under way.
More trials run by PfizerThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Masking: None (open label)
Enrolment: 101 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01597193
Sponsor's protocol ID: MDV3100-08
Other IDs: C3431006
Status last verified: May 2019
First submitted: 9 May 2012
Last updated: 8 May 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: 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.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 8 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A PHASE 1 OPEN-LABEL, DOSE ESCALATION STUDY EVALUATING THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF ENZALUTAMIDE (FORMERLY MDV3100) IN PATIENTS WITH INCURABLE BREAST CANCER
ClinicalTrials.gov ID: NCT01597193
Acronym / sponsor ID: MDV3100-08
Conditions: Breast Cancer
Keywords: enzalutamide, MDV3100, breast cancer
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 101 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Collaborators: Astellas Pharma Inc, Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Study start: 30 Apr 2012 (actual)
Primary completion: 15 Dec 2015 (actual)
Study completion: 22 Jan 2018 (actual)
First posted: 11 May 2012 (estimated)
Results: Posted 8 May 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
enzalutamide (80-mg with increase to 160 mg)	Experimental	Drug: enzalutamideenzalutamide be provided as two or four 40-mg capsules by mouth daily
enzalutamide and anastrozole	Experimental	Drug: anastrozole, Drug: enzalutamideenzalutamide (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	Experimental	Drug: exemestane, Drug: enzalutamideenzalutamide (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	Experimental	Drug: enzalutamide, Drug: exemestaneenzalutamide (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	Experimental	Drug: fulvestrant, Drug: enzalutamideenzalutamide (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

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (5 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
enzalutamideAlso: MDV3100, Xtandi80 mg (2 capsules) or 160 mg (4 capsules) taken orally daily.	Drug	enzalutamide (80-mg with increase to 160 mg)
anastrozoleAlso: Arimidex1 mg/day	Drug	enzalutamide and anastrozole
exemestaneAlso: AromasinThe exemestane dose is 25mg daily.	Drug	enzalutamide and exemestane 25 mg
fulvestrantAlso: Faslodex500 mg every 28 days	Drug	enzalutamide and fulvestrant
enzalutamideAlso: MDV3100, Xtandi160 mg (4 capsules) taken orally daily.	Drug	enzalutamide and anastrozole, enzalutamide and exemestane 25 mg, enzalutamide and exemestane 50 mg, enzalutamide and fulvestrant
exemestaneAlso: AromasinThe exemestane dose is 50 mg daily.	Drug	enzalutamide and exemestane 50 mg

Primary outcome

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

1 secondary outcome

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

Results and safety

Results posted to the registry on 8 May 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dose Escalation: Enzalutamide 80 mg	7	0
Dose Escalation: Enzalutamide 160 mg	8	0
Dose Expansion: Enzalutamide 160 mg	0	0
Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg	0	0
Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg	0	0
Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg	0	0
Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg	0	0

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

Time frame: Baseline up to Day 35. Number. Unit: percentage of participants

Measure	Dose Escalation: Enzalutamide 80 mg n = 6	Dose Escalation: Enzalutamide 160 mg n = 7
Value	16.7	0.0

Population analysed: 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.

Primary outcome: 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)

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). Number. Unit: percentage of participants

Measure	Dose Escalation: Enzalutamide 80 mg n = 7	Dose Escalation: Enzalutamide 160 mg n = 8	Dose Expansion: Enzalutamide 160 mg n = 14	Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg n = 20	Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg n = 16	Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg n = 23	Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg n = 11
Value	57.1	12.5	21.4	30.0	37.5	39.1	36.4

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

Primary outcome: Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)

Measure	Dose Escalation: Enzalutamide 80 mg n = 7	Dose Escalation: Enzalutamide 160 mg n = 8	Dose Expansion: Enzalutamide 160 mg n = 14	Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg n = 20	Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg n = 16	Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg n = 23	Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg n = 11
Value	28.6	12.5	14.3	5.0	31.3	13.0	18.2

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

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

Measure	Dose Escalation: Enzalutamide 80 mg n = 7	Dose Escalation: Enzalutamide 160 mg n = 8	Dose Expansion: Enzalutamide 160 mg n = 14	Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg n = 20	Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg n = 16	Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg n = 23	Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg n = 11
Value	0.0	0.0	7.1	5.0	12.5	13.0	0.0

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

1 secondary outcome is reported in the full results.

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). Other adverse events reported at 5% frequency or more

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

Limitations and caveats (from the sponsor): Prioritization of outcome measures as primary and secondary was based on the study team's discretion.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Pfizer Pfizer CT.gov Call Center study director

Pfizer

17 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing enzalutamide, anastrozole and exemestane in people with Breast Cancer, run by Pfizer at 17 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-Escalation Phase: Percentage of Participants With Dose-limiting Toxicity (DLTs) (time frame: Baseline up to Day 35). The study lists 20 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01597193.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2019; AzTrials last refreshed its copy on 8 Nov 2026.