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

Primary Purpose

Metastatic Progressive Castration-resistant Prostate Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Enzalutamide
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Progressive Castration-resistant Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Enzalutamide

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.
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.
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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
Change From Baseline in Urinary N-Telopeptide
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.
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.
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.
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.

Full Information

First Posted
March 19, 2010
Last Updated
October 19, 2018
Sponsor
Pfizer
Collaborators
Astellas Pharma Inc, Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01091103
Brief Title
Determine Effect of Enzalutamide (MDV3100) on the Androgen Signaling Pathway in Correlation With the Anti-tumor Effects of Enzalutamide
Official Title
A Study Of Continuous Oral Dosing Of A Novel Antiandrogen Mdv3100, In Castration-resistant Bone Metastatic Prostate Cancer Patients Evaluating The Tumor Micro-enviroment
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
February 18, 2010 (Actual)
Primary Completion Date
February 29, 2012 (Actual)
Study Completion Date
August 31, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
Collaborators
Astellas Pharma Inc, Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Progressive Castration-resistant Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Enzalutamide
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Enzalutamide
Other Intervention Name(s)
MDV3100
Primary Outcome Measure Information:
Title
Change From Baseline in Bone Marrow Testosterone
Description
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.
Time Frame
Baseline, Week 9
Title
Change From Baseline in Bone Marrow Dihydrotestosterone
Description
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.
Time Frame
Baseline, Week 9
Title
Change From Baseline in Bone Marrow Testosterone at Week 9 by Prostate-Specific Antigen (PSA) Response Status
Description
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.
Time Frame
Baseline, Week 9
Title
Change From Baseline in Bone Marrow Dihydrotestosterone at Week 9 by Prostate-Specific Antigen (PSA) Response Status
Description
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.
Time Frame
Baseline, Week 9
Secondary Outcome Measure Information:
Title
Percentage of Participants at Week 9 With a Response in Prostate-Specific Antigen (PSA)
Description
Serum samples for measurement of PSA levels were obtained at baseline prior to initiation of enzalutamide administration and at the Week 9 visit.
Time Frame
Baseline, Week 9
Title
Median Time to Study Drug Discontinuation
Description
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.
Time Frame
Duration of study treatment through the data cutoff, up to 3 years.
Title
Change From Baseline in Urinary N-Telopeptide
Description
Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 5.
Time Frame
Baseline, Week 5
Title
Change From Baseline in Urinary N-Telopeptide
Description
Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 9.
Time Frame
Baseline, Week 9
Title
Change From Baseline in Urinary N-Telopeptide
Description
Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 17.
Time Frame
Baseline, Week 17
Title
Change From Baseline in Urinary N-Telopeptide
Description
Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 25.
Time Frame
Baseline, Week 25
Title
Change From Baseline in Urinary N-Telopeptide
Time Frame
Baseline, Week 33
Title
Change From Baseline in Urinary N-Telopeptide
Description
Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 41.
Time Frame
Baseline, Week 41
Title
Change From Baseline in Urinary N-Telopeptide
Description
Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 49.
Time Frame
Baseline, Week 49
Title
Change From Baseline in Urinary N-Telopeptide
Description
Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 57.
Time Frame
Baseline, Week 57
Title
Change From Baseline in Urinary N-Telopeptide
Description
Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 65.
Time Frame
Baseline, Week 65

10. Eligibility

Sex
Male
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Medivation, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77303
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24882673
Citation
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.
Results Reference
derived

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

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