Phase 1 Completed N=15 Treatment

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

Source: ClinicalTrials.gov NCT01597193 ↗

Enrolled (actual)

Serious AEs

16.2%

Results posted

May 2019

Primary outcomePrimary: Dose-Escalation Phase: Percentage of Participants With Dose-limiting Toxicity (DLTs) — 16.7; 0.0 percentage of participants

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.

Outcome Measures

Outcome	Result	p-value
PRIMARY Dose-Escalation Phase: Percentage of Participants With Dose-limiting Toxicity (DLTs)	16.7; 0.0	—
PRIMARY 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	—
PRIMARY Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)	28.6; 12.5; 14.3; 5.0; 31.3; 13.0	—
PRIMARY 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	—
PRIMARY Percentage of Participants Who Require Dose Reductions Due to Adverse Events	0.0; 0.0; 0.0; 20.0; 12.5; 8.7	—
PRIMARY Percentage of Participants With Potentially Clinically Significant Change From Baseline in Vital Signs	1; 0; 1; 0; 1; 2	—
PRIMARY Dose-Escalation Phase: Maximum Plasma Concentration (Cmax) of Enzalutamide and Its Metabolites After Single Dose	1.90; 4.01; 0.0375; 0.0707; 0.0879; 0.184	—
PRIMARY Dose-Escalation Phase: Time to Reach Maximum Plasma Concentration (Tmax) of Enzalutamide and Its Metabolites After Single Dosing	0.500; 1.00; 24.1; 23.1; 23.9; 23.7	—
PRIMARY 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	17.3; 41.6; 0.632; 1.20; 1.13; 2.76	—
PRIMARY Dose-Escalation Phase: Area Under the Plasma Concentration-time Curve From Time Zero to 72 Hours (AUC72h) of Enzalutamide After Single Dosing	43.0; 107	—
PRIMARY Dose-Escalation Phase: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Enzalutamide After Single Dosing	208; 478	—
PRIMARY Dose-Escalation Phase: Terminal Elimination Half-Life (t1/2) of Enzalutamide After Single Dosing	280; 198	—
PRIMARY Dose Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Single Dosing	0.426; 0.382	—
PRIMARY Dose Escalation Phase: Apparent Volume of Distribution (Vz/F) of Enzalutamide After Single Dosing	151; 94.5	—
PRIMARY Dose-Escalation Phase: Maximum Plasma Concentration (Cmax) of Enzalutamide and Its Metabolites After Multiple Dosing	11.6; 15.3; 1.77; 6.24; 6.42; 14.1	—
PRIMARY Dose-Escalation Phase: Time to Reach Maximum Plasma Concentration (Tmax) of Enzalutamide and Its Metabolites After Multiple Dosing	0.500; 1.00; 5.70; 2.29; 24.0; 0.58	—
PRIMARY Dose-Escalation Phase: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Enzalutamide and Its Metabolites After Multiple Dosing	207; 325; 33.0; 120; 140; 317	—
PRIMARY Dose-Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Multiple Dosing	0.390; 0.507	—
PRIMARY Dose-Escalation Phase: Peak-to-Trough Ratio of Enzalutamide and Its Metabolites After Multiple Dosing	1.39; 1.14; 1.32; 1.42; 0.999; 1.00	—
PRIMARY Dose-Escalation Phase: Accumulation Ratio of AUC24 of Enzalutamide and Its Metabolites After Multiple Dosing	17.9; 9.39; 47.6; 68.0; 157; 77.8	—
SECONDARY Dose-Expansion Phase: Trough Plasma Concentration for Enzalutamide	13.40; 14.33; 13.52; 12.41; 11.62	—

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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01597193). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.