Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Abiraterone Acetate

Prednisone

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Participants received enzalutamide combined with abiraterone acetate once daily plus prednisone twice daily.

Participants received 160 mg of enzalutamide orally once daily (4 capsules, 40 mg each).

enzalutamide

Participants received 1000 mg of abiraterone acetate orally once daily (4 tablets, 250 mg each).

abiraterone acetate

Participants received 5 mg of prednisone orally twice daily (2 tablets, 5 mg each).

prednisone

Associate Medical Director

The purpose of this study was to explore the safety and tolerability of enzalutamide in combination with abiraterone acetate plus prednisone. Subjects diagnosed with cancer of the prostate that was getting worse and spreading to the bone despite receiving hormone treatment were enrolled and received study treatment until disease progression.

For the study duration, all subjects maintained androgen deprivation with a gonadotropin releasing hormone (GnRH) agonist or antagonist or orchiectomy. Study drug was administered until disease progression. Disease progression was defined as a composite endpoint consisting of either clinical deterioration, radiographic progression or prostate-specific antigen (PSA) progression according to the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria.

A Study to Determine Safety and Tolerability of Enzalutamide (MDV3100) in Combination With Abiraterone Acetate in Bone Metastatic Castration-Resistant Prostate Cancer Patients

A Phase 2 Study Determining Safety and Tolerability of Enzalutamide (Formerly MDV3100) in Combination With Abiraterone Acetate in Bone Metastatic Castration-Resistant Prostate Cancer Patients

Access to anonymized individual participant level data collected during the trial, in addition to study-related supporting documentation, is planned for trials conducted with approved product indications and formulations, as well as compounds terminated during development. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

The endpoint was considered exploratory and no analysis was planned.

A treatment-emergent adverse event (TEAE) was defined as an adverse event occurring or worsening between the start of study treatment date and the latest date of 30 days after the last dose date or the 30-day follow-up visit date, and not later than the data cut-off date or the date of death. AEs, including abnormal clinical laboratory values, were graded using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) guidelines (V4.03).

Testosterone concentration in bone marrow aspirate was measured by laboratory results derived from bone marrow samples processed through liquid chromatography mass spectrometry.

DHT concentration in bone marrow aspirate was to be measured by laboratory results derived from bone marrow samples processed through liquid chromatography mass spectrometry. DHT bone data were not collected.

Cortisol in bone marrow aspirate was measured by laboratory results derived from bone marrow samples.

Androstenedione in bone marrow aspirate was measured by laboratory results derived from bone marrow samples.

Progesterone in bone marrow aspirate was measured by laboratory results derived from bone marrow samples.

Pregnenolone in bone marrow aspirate was measured by laboratory results derived from bone marrow samples.

Testosterone concentration in blood was measured by laboratory results derived from plasma samples. Plasma samples were derived from collected blood samples processed through liquid chromatography mass spectrometry.

DHT concentration in blood was measured by laboratory results derived from plasma samples. Plasma samples were derived from collected blood samples processed through liquid chromatography mass spectrometry. The endpoint could not be analyzed since no participants had DHT levels over the lower limit of quantification (LLOQ).

Cortisol concentration in blood was measured by laboratory results derived from plasma samples. Plasma samples were derived from collected blood samples processed through liquid chromatography mass spectrometry.

Androstenedione concentration in blood was measured by laboratory results derived from plasma samples. Plasma samples were derived from collected blood samples processed through liquid chromatography mass spectrometry.

Progesterone concentration in blood was measured by laboratory results derived from plasma samples. Plasma samples were derived from collected blood samples processed through liquid chromatography mass spectrometry.

Pregnenolone concentration in blood was measured by laboratory results derived from plasma samples. Plasma samples were derived from collected blood samples processed through liquid chromatography mass spectrometry.

Prostate-specific antigen progression by Prostate Cancer Clinical Trials Working Group 2 (PCWG2) was defined as a PSA increase ≥25% and ≥2 ng/ml above the post-baseline nadir, and which was confirmed by the first subsequent value of 3 or more weeks later.

PFS was measured as the time from the date of first dose of any drug of the study combination treatment until the first evidence of documented progression (a composite endpoint consisting of radiographic progression or PSA progression by PCWG2 or clinical deterioration) or death in the absence of progression (whichever came first) or the date last known to be progression free. The Kaplan-Meier (KM) 95% CI was based on Brookmeyer and Crowley robust non-parametric method.

Objective response was based on RECIST version 1.1 for soft tissue lesion on Magnetic resonance imaging (MRI) / Computerized tomography (CT) and the PCWG2 guidelines for bone lesions on bone scans and was defined as partial response (PR) or complete response (CR) based on the investigators' assessments of target, non-target and new lesions while on study treatment. The 95% for objective response rate was based on exact binomial 95% confidence interval (Clopper-Pearson).

PD: ≥1 of 3 criteria: PSA progression: ≥2 rising PSA levels, interval of ≥1 week between each determination. Soft tissue disease progression: RECIST 1.1. Bone disease progression: PCWG2 criteria (≥2 or new lesions on bone scan compared with prior scan). Target lesion CR: disappearance of all target lesions, PR as ≥30% decrease in sum of longest diameter (LD) of target lesions, referencing baseline sum LD, SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, referencing smallest sum LD since treatment start, PD ≥20% increase in sum of LD of target lesions, referencing smallest sum LD recorded since treatment start or appearance of ≥1 new lesions. Non-target lesions CR: disappearance of all non-target lesions and normalization of tumor marker level, SD: persistence of ≥1 non-target lesions and/or maintenance of tumor marker level above normal limits, PD: appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions.

Bone metabolism marker bone specific alkaline phosphatase levels were derived from blood samples collected.

Bone metabolism marker urine N-telopeptide levels were derived from urine samples collected.

Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

Astellas Pharma Global Development, Inc.

Enzalutamide + Abiraterone + Prednisone

Age, Continuous

Sex: Female, Male

White

Black or African American

Asian

Other

Race/Ethnicity, Customized

Not Hispanic or Latino

Hispanic or Latino

Ethnicity

The analysis population for all baseline measures consisted of all participants who were enrolled in the study.

Clinical Trial Disclosure

Any TEAE

Enzalutamide-related TEAEs

Abiraterone-related TEAEs

Prednisone-related TEAEs

Deaths

Serious TEAEs

Enzalutamide-related serious TEAEs

Abiraterone-related serious TEAEs

Prednisone-related serious TEAEs

TEAEs leading to discontinuation of enzalutamide

Enza-related TEAEs leading to disc. of enza

Abiraterone-related TEAEs leading to disc. of enza

Prednisone-related TEAEs leading to disc. of enza

TEAEs leading to discontinuation of abiraterone

Abiraterone-related TEAEs leading to disc. of abi

The analysis population consisted of the safety analysis set (SAF) which consisted of all participants who received at least 1 dose of any drug of the study combination treatment (i.e., enzalutamide, abiraterone and prednisone).

Number of Participants With Adverse Events (AEs)

Testosterone biomarker results collected at baseline and at Week 9 were compared using the paired t-test to evaluate the effect of enzalutamide.

The analysis population consisted of the biomarker testosterone evaluable set (BTES) which consisted of all participants from the SAF with baseline and week 9 testosterone laboratory results derived from bone marrow samples.

Change From Baseline in Testosterone Concentration in Bone Marrow Aspirate

Participants received enzalutamide combined with abiraterone acetate once daily plus prednisone twice daily. DHT bone data were not collected.

Change From Baseline in Dihydrotestosterone (DHT) Concentration in Bone Marrow Aspirate

Cortisol biomarker results collected at baseline and at Week 9 were compared using the paired t-test to evaluate the effect of enzalutamide.

The analysis population consisted of the biomarker cortisol evaluable set (BCES) which consisted of all participants from the SAF with baseline and week 9 cortisol laboratory results derived from bone marrow samples.

Change From Baseline in Cortisol in Bone Marrow Aspirate

Androstenedione biomarker results collected at baseline and at Week 9 were compared using the paired t-test to evaluate the effect of enzalutamide.

The analysis population consisted of the biomarker androstenedione evaluable set (BAOS) which consisted of all participants from the SAF with baseline and week 9 androstenedione laboratory results derived from bone marrow samples.

Change From Baseline in Androstenedione in Bone Marrow Aspirate

Progesterone biomarker results collected at baseline and at Week 9 were compared using the paired t-test to evaluate the effect of enzalutamide.

The analysis population consisted of the biomarker progesterone evaluable set (BOES) which consisted of all participants from the SAF with baseline and week 9 progesterone laboratory results derived from bone marrow samples.

Change From Baseline in Progesterone in Bone Marrow Aspirate

Pregnenolone biomarker results collected at baseline and at Week 9 were compared using the paired t-test to evaluate the effect of enzalutamide.

The analysis population consisted of the biomarker pregnenolone evaluable set (BEES) which consisted of all participants from the SAF with baseline and week 9 pregnenolone laboratory results derived from bone marrow samples.

Change From Baseline in Pregnenolone in Bone Marrow Aspirate

Testosterone blood results collected at baseline and at Week 9 were compared using the paired t-test to evaluate the effect of enzalutamide.

The analysis population consisted of the plasma testosterone evaluable set (PTES) which consisted of all participants from the SAF with baseline and week 9 testosterone laboratory results derived from plasma samples.

Change From Baseline in Testosterone Concentration in Blood

The endpoint could not be analyzed since no participants had DHT levels over the LLOQ.

Change From Baseline in DHT Concentration in Blood

Cortisol blood results collected at baseline and at Week 9 were compared using the paired t-test to evaluate the effect of enzalutamide.

The analysis population consisted of the plasma cortisol evaluable set (PCES) which consisted of all participants from the SAF with baseline and week 9 cortisol laboratory results derived from plasma samples.

Change From Baseline in Cortisol Concentration in Blood

Androstenedione blood results collected at baseline and at Week 9 were compared using the paired t-test to evaluate the effect of enzalutamide.

The analysis population consisted of the plasma androstenedione evaluable set (PAOS) which consisted of all participants from the SAF with baseline and week 9 androstenedione laboratory results derived from plasma samples.

Change From Baseline in Androstenedione Concentration in Blood

Progesterone blood results collected at baseline and at Week 9 were compared using the paired t-test to evaluate the effect of enzalutamide.

The analysis population consisted of the plasma progesterone evaluable set (POES) which consisted of all participants from the SAF with baseline and week 9 progesterone laboratory results derived from plasma samples.

Change From Baseline in Progesterone Concentration in Blood

Pregnenolone blood results collected at baseline and at Week 9 were compared using the paired t-test to evaluate the effect of enzalutamide.

The analysis population consisted of the plasma pregnenolone evaluable set (PEES) which consisted of all participants from the SAF with baseline and week 9 pregnenolone laboratory results derived from plasma samples.

Change From Baseline in Pregnenolone Concentration in Blood

The analysis population consisted of the SAF (participants with available data).

Change From Baseline to End-of-Treatment (EoT) in Prostate-Specific Antigen (PSA) Levels

The analysis population consisted of the SAF.

Progression Free Survival (PFS)

The analysis population consisted of the SAF (participants with measurable soft tissue disease per RECIST 1.1 at baseline with available data).

Percentage of Participants With Objective Response for Soft Tissue Lesions According to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST)

Complete Response (CR)

Progressive Disease (PD)

Non-CR/Non-PD

Not Evaluable

Bone Scan Response at EoT

Change From Baseline to EoT in Bone Specific Alkaline Phosphatase

Change From Baseline in Urine N-Telopeptide

Data for these endpoints were not collected.

Androgen Receptor Signaling Assessed by Expression and Localization of Androgen Receptor (AR), CYP17 Expression, Splice Variants, and Pathways Linked With Non-classical AR Signaling and Bone Development

Spots Global Cancer Trial Database for A Study to Determine Safety and Tolerability of Enzalutamide (MDV3100) in Combination With Abiraterone Acetate in Bone Metastatic Castration-Resistant Prostate Cancer Patients

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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