Determine Effect of Enzalutamide (MDV3100) on the Androgen Signaling Pathway in Correlation With the Anti-tumor Effects of Enzalutamide

A Study Of Continuous Oral Dosing Of A Novel Antiandrogen Mdv3100, In Castration-resistant Bone Metastatic Prostate Cancer Patients Evaluating The Tumor Micro-enviroment

This study is being conducted to determine the effect of enzalutamide on the androgen signaling pathway in correlation with the anti-tumor effects of enzalutamide to identify potential predictors of response or resistance to therapy.

Study Overview

• Status: Completed
• Conditions: Metastatic Progressive Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: Enzalutamide

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77303
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Confirmed prostate cancer
• Presence of metastatic disease to the bone
• Ongoing androgen deprivation therapy

Exclusion Criteria:

• Severe concurrent disease
• Metastases in the brain

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enzalutamide; Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth. Study drug treatment continued until disease progression, unacceptable toxicity, or withdrawal.	Drug: Enzalutamide; Other Names: MDV3100

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Bone Marrow Testosterone	Bone marrow biopsies were performed at the Day 1 visit prior to initiation of enzalutamide administration. Repeat bone marrow biopsies were performed at the Week 9 visit. If a repeat bone marrow was not performed at the Week 9 visit or if a patient discontinued the study before the Week 9 visit, a bone marrow biopsy was obtained at the Safety Follow-up visit. Assessment of intratumoral testosterone was assessed by liquid chromatography mass spectrometry.	Baseline, Week 9
Change From Baseline in Bone Marrow Dihydrotestosterone	Bone marrow biopsies were performed at the Day 1 visit prior to initiation of enzalutamide administration. Repeat bone marrow biopsies were performed at the Week 9 visit. If a repeat bone marrow was not performed at the Week 9 visit or if a patient discontinued the study before the Week 9 visit, a bone marrow biopsy was obtained at the Safety Follow-up visit. Assessment of intratumoral dihydrotestosterone was assessed by liquid chromatography mass spectrometry.	Baseline, Week 9
Change From Baseline in Bone Marrow Testosterone at Week 9 by Prostate-Specific Antigen (PSA) Response Status	Bone marrow biopsies were performed at the Day 1 visit prior to initiation of enzalutamide administration. Repeat bone marrow biopsies were performed at the Week 9 visit. If a repeat bone marrow was not performed at the Week 9 visit or if a patient discontinued the study before the Week 9 visit, a bone marrow biopsy was obtained at the Safety Follow-up visit. Assessment of intratumoral testosterone was assessed by liquid chromatography mass spectrometry. Serum samples for measurement of PSA levels were obtained at baseline prior to initiation of enzalutamide administration and at the Week 9 visit. The change from baseline in bone marrow testosterone levels at Week 9 was correlated with PSA response status at Week 9.	Baseline, Week 9
Change From Baseline in Bone Marrow Dihydrotestosterone at Week 9 by Prostate-Specific Antigen (PSA) Response Status	Bone marrow biopsies were performed at the Day 1 visit prior to initiation of enzalutamide administration. Repeat bone marrow biopsies were performed at the Week 9 visit. If a repeat bone marrow was not performed at the Week 9 visit or if a patient discontinued the study before the Week 9 visit, a bone marrow biopsy was obtained at the Safety Follow-up visit. Assessment of intratumoral dihydrotestosterone was assessed by liquid chromatography mass spectrometry. Serum samples for measurement of PSA levels were obtained at baseline prior to initiation of enzalutamide administration and at the Week 9 visit. The change from baseline in bone marrow dihydrotestosterone levels at Week 9 was correlated with PSA response status at Week 9.	Baseline, Week 9

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants at Week 9 With a Response in Prostate-Specific Antigen (PSA)	Serum samples for measurement of PSA levels were obtained at baseline prior to initiation of enzalutamide administration and at the Week 9 visit.	Baseline, Week 9
Median Time to Study Drug Discontinuation	Exposure to study drug through the data cutoff of 26AUG2011 only. Fifteen participants (25.0%) were still on study drug as of the data cut-off date and were censored at this date.	Duration of study treatment through the data cutoff, up to 3 years.
Change From Baseline in Urinary N-Telopeptide	Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 5.	Baseline, Week 5
Change From Baseline in Urinary N-Telopeptide	Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 9.	Baseline, Week 9
Change From Baseline in Urinary N-Telopeptide	Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 17.	Baseline, Week 17
Change From Baseline in Urinary N-Telopeptide	Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 25.	Baseline, Week 25
Change From Baseline in Urinary N-Telopeptide		Baseline, Week 33
Change From Baseline in Urinary N-Telopeptide	Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 41.	Baseline, Week 41
Change From Baseline in Urinary N-Telopeptide	Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 49.	Baseline, Week 49
Change From Baseline in Urinary N-Telopeptide	Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 57.	Baseline, Week 57
Change From Baseline in Urinary N-Telopeptide	Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 65.	Baseline, Week 65

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Astellas Pharma Inc; Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
• Investigators: Study Director: Medical Monitor, Medivation, Inc.

Publications and helpful links

General Publications

• Efstathiou E, Titus M, Wen S, Hoang A, Karlou M, Ashe R, Tu SM, Aparicio A, Troncoso P, Mohler J, Logothetis CJ. Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. Eur Urol. 2015 Jan;67(1):53-60. doi: 10.1016/j.eururo.2014.05.005. Epub 2014 May 29.

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2010
• Primary Completion (Actual): February 29, 2012
• Study Completion (Actual): August 31, 2013

Study Registration Dates

• First Submitted: March 19, 2010
• First Submitted That Met QC Criteria: March 22, 2010
• First Posted (Estimate): March 23, 2010

Study Record Updates

• Last Update Posted (Actual): October 23, 2018
• Last Update Submitted That Met QC Criteria: October 19, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: CRPC-MDA-1; C3431017 (Other Identifier: Alias Study Number)