Clinical trial NCT01597193: Safety Study of Enzalutamide (MDV3100) in Patients With Incurable Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Keywords: enzalutamide
MDV3100
breast cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Astellas Pharma Inc
name: Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
First posted: 2012-05-11
Enrollment: 101
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety, tolerability and pharmacokinetics of enzalutamide alone and in combination with anastrozole, or exemestane, or fulvestrant in patients with incurable breast cancer.


Eligibility criteria: 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:

* 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.

Primary outcomes:
measure: Dose-Escalation Phase: Percentage of Participants With Dose-limiting Toxicity (DLTs)
timeFrame: Baseline up to Day 35
measure: 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)
timeFrame: 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)
measure: Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
timeFrame: 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)
measure: Percentage of Participants Who Discontinued the Study Drug Due to Adverse Events or Serious Adverse Events
timeFrame: 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)
measure: Percentage of Participants Who Require Dose Reductions Due to Adverse Events
timeFrame: 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)
measure: Percentage of Participants With Potentially Clinically Significant Change From Baseline in Vital Signs
timeFrame: 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)
measure: Dose-Escalation Phase: Maximum Plasma Concentration (Cmax) of Enzalutamide and Its Metabolites After Single Dose
timeFrame: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1
measure: Dose-Escalation Phase: Time to Reach Maximum Plasma Concentration (Tmax) of Enzalutamide and Its Metabolites After Single Dosing
timeFrame: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1
measure: 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
timeFrame: pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post dose on Day 1
measure: Dose-Escalation Phase: Area Under the Plasma Concentration-time Curve From Time Zero to 72 Hours (AUC72h) of Enzalutamide After Single Dosing
timeFrame: pre-dose, 0.5, 1, 2, 4, 6, 24, 48 and 72 hours post dose on Day 1
measure: Dose-Escalation Phase: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Enzalutamide After Single Dosing
timeFrame: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1
measure: Dose-Escalation Phase: Terminal Elimination Half-Life (t1/2) of Enzalutamide After Single Dosing
timeFrame: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1
measure: Dose Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Single Dosing
timeFrame: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1
measure: Dose Escalation Phase: Apparent Volume of Distribution (Vz/F) of Enzalutamide After Single Dosing
timeFrame: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1
measure: Dose-Escalation Phase: Maximum Plasma Concentration (Cmax) of Enzalutamide and Its Metabolites After Multiple Dosing
timeFrame: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50
measure: Dose-Escalation Phase: Time to Reach Maximum Plasma Concentration (Tmax) of Enzalutamide and Its Metabolites After Multiple Dosing
timeFrame: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50
measure: Dose-Escalation Phase: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Enzalutamide and Its Metabolites After Multiple Dosing
timeFrame: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50
measure: Dose-Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Multiple Dosing
timeFrame: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50
measure: Dose-Escalation Phase: Peak-to-Trough Ratio of Enzalutamide and Its Metabolites After Multiple Dosing
timeFrame: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50
measure: Dose-Escalation Phase: Accumulation Ratio of AUC24 of Enzalutamide and Its Metabolites After Multiple Dosing
timeFrame: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 1 and 50
Secondary outcomes:
measure: Dose-Expansion Phase: Trough Plasma Concentration for Enzalutamide
timeFrame: pre-dose on Day 57
Other outcomes:
Locations:
city: Aurora
country: United States
facility: ATTN-Research Pharmacist
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital, Anschutz Outpatient Pavilion
state: Colorado
city: Enfield
country: United States
facility: Connecticut Multispecialty Group
state: Connecticut
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Corinth
country: United States
facility: The West Clinic, PC
state: Mississippi
city: Southaven
country: United States
facility: The West Clinic
state: Mississippi
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center - IDS Pharmacy
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center - OPD Pharmacy
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Germantown
country: United States
facility: The West Clinic
state: Tennessee
city: Memphis
country: United States
facility: The West Clinic
state: Tennessee
city: Memphis
country: United States
facility: The West Clinic
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC.
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute
state: Tennessee
Study officials:
affiliation: Pfizer
name: Pfizer Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: