Safety and Tolerability Study of MDV3100 in Combination With Docetaxel in Men With Advanced Prostate Cancer
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT01565928
Collaborator
Astellas Pharma Inc (Industry), Medivation LLC, a wholly owned subsidiary of Pfizer Inc. (Industry)
23
3
1
73.1
7.7
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is to determine the safety of MDV3100 given in combination with Docetaxel in men with advanced prostate cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
23 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A PHASE 1B, OPEN-LABEL, SAFETY AND TOLERABILITY STUDY OF ORAL MDV3100 IN COMBINATION WITH DOCETAXEL IN MEN WITH ADVANCED PROSTATE CANCER
Actual Study Start Date
:
Jan 24, 2012
Actual Primary Completion Date
:
Jul 1, 2013
Actual Study Completion Date
:
Feb 26, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MDV3100
|
Drug: MDV3100
4 x 40 mg capsules, orally, once per day
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Who Required Study Drug Dose Reduction During Treatment Periods 1 and 2 [Treatment Period 1 (Day 1) up to end of Treatment Period 2 (42 days)]
Percentage of participants that required dose reductions of Docetaxel and Enzalutamide treatment were reported in this outcome measure. Dose modifications (interruptions or dose reductions) were permitted for participants who had adverse events that were intolerable or could not be improved by other means. Dose reductions or delays were determined according to the prescribing information and at the discretion of the investigator.
- Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) [Treatment Period 1 (Day 1) up to end of study treatment (maximum 70 months)]
AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Percentage of participants that discontinued study drug due to adverse events were reported in this outcome measure.
Secondary Outcome Measures
- Number of Participants With Clinically Significant Abnormalities in Vital Signs [T1= Baseline (Day 1) up to a maximum of approximately Month 12; T2 = From Month 10.6 up to a maximum of approximately Month 71.5]
Criteria:1)systolic blood pressure (SBP):a) absolute result(AR)>=180millimeters of mercury(mmHg) and increase from baseline(BL)greater than(>)40mmHg,b)less than(<)90mmHg and decrease from BL>30mmHg,c)most extreme post-BL result>=140mmHg,d)most extreme post-BL result>=180mmHg,e)most extreme result(MER)>=180mmHg and >=20mmHg change from BL,f)MER>=140mmHg and >=20mmHg change from BL;2)diastolic blood pressure(DBP):a)AR>105mmHg and increase from BL,b)AR<50mmHg and decrease from BL>20mmHg;c)most extreme post-BL result>=90mmHg,d)MER>=90mmHg and >=15mmHg change from BL,e)most extreme post-BL result>=105mmHg,f)MER>=105mmHg and>=15mmHg change from BL;3)heart rate:a)AR>120 beats per minute(bpm) and increase from BL>30bpm,b) AR<50 bpm and decrease from BL>20bpm.Only those categories in which at least 1 participant had clinically significant vital sign abnormality, were reported in this outcome measure.T1 = Timeframe for "Combination Therapy" and T2 = Time frame for "Post-Docetaxel Enzalutamide".
- Number of Participants With Clinically Significant Change From Baseline in Electrocardiograms (ECG) [T1= Baseline (Day 1) up to a maximum of approximately Month 12; T2 = From Month 10.6 up to a maximum of approximately Month 71.5]
Clinically significant changes from baseline in ECG findings was based up on investigator's discretion. T1 = Timeframe for "Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg" and T2 = Time frame for "Post-Docetaxel Enzalutamide 160 mg".
- Maximum Plasma Concentration (Cmax) of Docetaxel With and Without Enzalutamide Treatment [Docetaxel without Enzalutamide: Predose, 0.5, 1, 1.5, 2, 4, 8 and 24 hour post docetaxel infusion on Day 1 of Treatment Period 1; Docetaxel with Enzalutamide: Predose, 0.5, 1, 1.5, 2, 4, 8 and 24 hour post docetaxel infusion on Day 1 of Treatment Period 2]
- Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of Docetaxel With and Without Enzalutamide Treatment [Docetaxel without Enzalutamide: Predose, 0.5, 1, 1.5, 2, 4, 8 and 24 hour post docetaxel infusion on Day 1 of Treatment Period 1; Docetaxel with Enzalutamide: Predose, 0.5, 1, 1.5, 2, 4, 8 and 24 hour post docetaxel infusion on Day 1 of Treatment Period 2]
AUClast was observed using a linear mixed-effects model.
- Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of Docetaxel With and Without Enzalutamide Treatment [Docetaxel without Enzalutamide: Predose, 0.5, 1, 1.5, 2, 4, 8 and 24 hour post docetaxel infusion on Day 1 of Treatment Period 1; Docetaxel with Enzalutamide: Predose, 0.5, 1, 1.5, 2, 4, 8 and 24 hour post docetaxel infusion on Day 1 of Treatment Period 2]
AUCinf was observed using a linear mixed-effects model.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Willing and able to provide informed consent;
-
Men, 18 years of age or older;
-
Histologically or cytologically confirmed adenocarcinoma of the prostate;
-
Ongoing androgen deprivation therapy
Exclusion Criteria:
-
Severe concurrent disease;
-
Known or suspected brain metastasis;
-
History of another malignancy within the previous 5 years;
-
Prior treatment with docetaxel-based chemotherapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 2 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10065 |
| 3 | Virginia Oncology Associates | Norfolk | Virginia | United States | 23502 |
Sponsors and Collaborators
- Pfizer
- Astellas Pharma Inc
- Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Investigators
- Study Director: Pfizer Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01565928
Other Study ID Numbers:
- MDV3100-06
- C3431002
First Posted:
Mar 29, 2012
Last Update Posted:
Apr 22, 2019
Last Verified:
Jan 1, 2019
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Docetaxel 75 mg/m^2+ Enzalutamide 160 mg |
|---|---|
| Arm/Group Description | Docetaxel 75 milligrams per square meter (mg/m^2) was administered as intravenous (IV) infusion for 1 hour on Day 1 of each treatment period (each treatment period was of 21 days). From Day 2 of treatment period 1, participants received a single oral dose of Enzalutamide (MDV3100) 160 milligrams (mg) (4 capsules of 40 mg each) once daily. Participants received a single oral dose of Dexamethasone 8 mg prior to each Docetaxel infusion and Prednisone (5 mg) once daily on the days of Docetaxel administration then twice daily every day thereafter as long as Docetaxel treatment continued. Participants who tolerated treatment with Docetaxel and Enzalutamide continued to receive the combined therapy. Participants who discontinued Docetaxel were allowed to continue the treatment with Enzalutamide 160 mg once daily up to the end of study treatment (maximum of Month 70). |
| Period Title: Overall Study | |
| STARTED | 22 |
| COMPLETED | 0 |
| NOT COMPLETED | 22 |
Baseline Characteristics
| Arm/Group Title | Docetaxel 75 mg/m^2+ Enzalutamide 160 mg |
|---|---|
| Arm/Group Description | Docetaxel 75 milligrams per square meter (mg/m^2) was administered as intravenous (IV) infusion for 1 hour on Day 1 of each treatment period (each treatment period was of 21 days). From Day 2 of treatment period 1, participants received a single oral dose of Enzalutamide (MDV3100) 160 milligrams (mg) (4 capsules of 40 mg each) once daily. Participants received a single oral dose of Dexamethasone 8 mg prior to each Docetaxel infusion and Prednisone (5 mg) once daily on the days of Docetaxel administration then twice daily every day thereafter as long as Docetaxel treatment continued. Participants who tolerated treatment with Docetaxel and Enzalutamide continued to receive the combined therapy. Participants who discontinued Docetaxel were allowed to continue the treatment with Enzalutamide 160 mg once daily up to the end of study treatment (maximum of Month 70). |
| Overall Participants | 22 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
68.0
(10.66)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
0
0%
|
| Male |
22
100%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
0
0%
|
| Not Hispanic or Latino |
22
100%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
3
13.6%
|
| White |
19
86.4%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
Outcome Measures
| Title | Percentage of Participants Who Required Study Drug Dose Reduction During Treatment Periods 1 and 2 |
|---|---|
| Description | Percentage of participants that required dose reductions of Docetaxel and Enzalutamide treatment were reported in this outcome measure. Dose modifications (interruptions or dose reductions) were permitted for participants who had adverse events that were intolerable or could not be improved by other means. Dose reductions or delays were determined according to the prescribing information and at the discretion of the investigator. |
| Time Frame | Treatment Period 1 (Day 1) up to end of Treatment Period 2 (42 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all enrolled participants who received at least 1 dose or partial dose of study drug (Enzalutamide and/or Docetaxel). |
| Arm/Group Title | Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg |
|---|---|
| Arm/Group Description | Docetaxel 75 mg/m^2 was administered as IV infusion for 1 hour on Day 1 in each treatment period (each treatment period was of 21 days). From Day 2 of treatment Period 1 participants received a single oral dose of Enzalutamide 160 mg once daily. Participants received a single oral dose of Dexamethasone 8 mg prior to each Docetaxel infusion and Prednisone 5 mg once daily on the days of docetaxel administration then twice daily every day thereafter as long as docetaxel treatment continued. Participants who tolerated treatment with Docetaxel and Enzalutamide received the both. |
| Measure Participants | 22 |
| Docetaxel Dose Reductions |
4.5
20.5%
|
| Enzalutamide Dose Reductions |
0.0
0%
|
| Title | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) |
|---|---|
| Description | AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Percentage of participants that discontinued study drug due to adverse events were reported in this outcome measure. |
| Time Frame | Treatment Period 1 (Day 1) up to end of study treatment (maximum 70 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all enrolled participants who received at least 1 dose or partial dose of study drug (Enzalutamide and/or Docetaxel). |
| Arm/Group Title | Docetaxel 75 mg/m^2+ Enzalutamide 160 mg |
|---|---|
| Arm/Group Description | Docetaxel 75 milligrams per square meter (mg/m^2) was administered as intravenous (IV) infusion for 1 hour on Day 1 of each treatment period (each treatment period was of 21 days). From Day 2 of treatment period 1, participants received a single oral dose of Enzalutamide (MDV3100) 160 milligrams (mg) (4 capsules of 40 mg each) once daily. Participants received a single oral dose of Dexamethasone 8 mg prior to each Docetaxel infusion and Prednisone (5 mg) once daily on the days of Docetaxel administration then twice daily every day thereafter as long as Docetaxel treatment continued. Participants who tolerated treatment with Docetaxel and Enzalutamide continued to receive the combined therapy. Participants who discontinued Docetaxel were allowed to continue the treatment with Enzalutamide 160 mg once daily up to the end of study treatment (maximum of Month 70). |
| Measure Participants | 22 |
| Number [percentage of participants] |
9.1
41.4%
|
| Title | Number of Participants With Clinically Significant Abnormalities in Vital Signs |
|---|---|
| Description | Criteria:1)systolic blood pressure (SBP):a) absolute result(AR)>=180millimeters of mercury(mmHg) and increase from baseline(BL)greater than(>)40mmHg,b)less than(<)90mmHg and decrease from BL>30mmHg,c)most extreme post-BL result>=140mmHg,d)most extreme post-BL result>=180mmHg,e)most extreme result(MER)>=180mmHg and >=20mmHg change from BL,f)MER>=140mmHg and >=20mmHg change from BL;2)diastolic blood pressure(DBP):a)AR>105mmHg and increase from BL,b)AR<50mmHg and decrease from BL>20mmHg;c)most extreme post-BL result>=90mmHg,d)MER>=90mmHg and >=15mmHg change from BL,e)most extreme post-BL result>=105mmHg,f)MER>=105mmHg and>=15mmHg change from BL;3)heart rate:a)AR>120 beats per minute(bpm) and increase from BL>30bpm,b) AR<50 bpm and decrease from BL>20bpm.Only those categories in which at least 1 participant had clinically significant vital sign abnormality, were reported in this outcome measure.T1 = Timeframe for "Combination Therapy" and T2 = Time frame for "Post-Docetaxel Enzalutamide". |
| Time Frame | T1= Baseline (Day 1) up to a maximum of approximately Month 12; T2 = From Month 10.6 up to a maximum of approximately Month 71.5 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all enrolled participants who received at least 1 dose or partial dose of study drug (Enzalutamide and/or Docetaxel). |
| Arm/Group Title | Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Post-Docetaxel Enzalutamide 160 mg |
|---|---|---|
| Arm/Group Description | Docetaxel 75 mg/m^2 was administered as IV infusion for 1 hour on Day 1 in each treatment period (each treatment period was of 21 days). From Day 2 of treatment Period 1 participants received a single oral dose of Enzalutamide 160 mg once daily. Participants received a single oral dose of Dexamethasone 8 mg prior to each Docetaxel infusion and Prednisone 5 mg once daily on the days of docetaxel administration then twice daily every day thereafter as long as docetaxel treatment continued. Participants who tolerated treatment with Docetaxel and Enzalutamide received the both. | Participants who had received the combination therapy of Docetaxel and Enzalutamide but discontinued the Docetaxel treatment and continued to receive a single oral dose of Enzalutamide 160 mg (4 capsule each of 40 mg) once daily up to the end of the study treatment (maximum of 70 months). |
| Measure Participants | 22 | 21 |
| SBP: AR- > 180 mmHg, increase from BL > 40 mmHg |
0
0%
|
1
NaN
|
| SBP: AR- < 90 mmHg, decrease from BL > 30 mmHg |
1
4.5%
|
0
NaN
|
| SBP: Most extreme post- BL result >= 140 mmHg |
10
45.5%
|
7
NaN
|
| SBP: Most extreme post- BL result >= 180 mmHg |
0
0%
|
2
NaN
|
| SBP: MER >= 180 mmHg, >= 20 mmHg change from BL |
0
0%
|
2
NaN
|
| SBP: MER >= 140 mmHg, >= 20 mmHg change from BL |
5
22.7%
|
5
NaN
|
| DBP: Most extreme post-BL result >= 90 mmHg |
3
13.6%
|
6
NaN
|
| DBP: Most extreme post-BL result >= 105 mmHg |
0
0%
|
1
NaN
|
| DBP: MER >= 105 mmHg,>= 15 mmHg change from BL |
0
0%
|
1
NaN
|
| DBP: MER >= 90 mmHg,>= 15 mmHg change from BL |
1
4.5%
|
4
NaN
|
| Heart Rate: AR >120 bpm, increase from BL >30 bpm |
0
0%
|
1
NaN
|
| Heart Rate: AR <50 bpm, decrease from BL >30 bpm |
0
0%
|
1
NaN
|
| Title | Number of Participants With Clinically Significant Change From Baseline in Electrocardiograms (ECG) |
|---|---|
| Description | Clinically significant changes from baseline in ECG findings was based up on investigator's discretion. T1 = Timeframe for "Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg" and T2 = Time frame for "Post-Docetaxel Enzalutamide 160 mg". |
| Time Frame | T1= Baseline (Day 1) up to a maximum of approximately Month 12; T2 = From Month 10.6 up to a maximum of approximately Month 71.5 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all enrolled participants who received at least 1 dose or partial dose of study drug (Enzalutamide and/or Docetaxel). |
| Arm/Group Title | Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Post-Docetaxel Enzalutamide 160 mg |
|---|---|---|
| Arm/Group Description | Docetaxel 75 mg/m^2 was administered as IV infusion for 1 hour on Day 1 in each treatment period (each treatment period was of 21 days). From Day 2 of treatment Period 1 participants received a single oral dose of Enzalutamide 160 mg once daily. Participants received a single oral dose of Dexamethasone 8 mg prior to each Docetaxel infusion and Prednisone 5 mg once daily on the days of docetaxel administration then twice daily every day thereafter as long as docetaxel treatment continued. Participants who tolerated treatment with Docetaxel and Enzalutamide received the both. | Participants who had received the combination therapy of Docetaxel and Enzalutamide but discontinued the Docetaxel treatment and continued to receive a single oral dose of Enzalutamide 160 mg (4 capsule each of 40 mg) once daily up to the end of the study treatment (maximum of 70 months). |
| Measure Participants | 22 | 21 |
| Count of Participants [Participants] |
1
4.5%
|
0
NaN
|
| Title | Maximum Plasma Concentration (Cmax) of Docetaxel With and Without Enzalutamide Treatment |
|---|---|
| Description | |
| Time Frame | Docetaxel without Enzalutamide: Predose, 0.5, 1, 1.5, 2, 4, 8 and 24 hour post docetaxel infusion on Day 1 of Treatment Period 1; Docetaxel with Enzalutamide: Predose, 0.5, 1, 1.5, 2, 4, 8 and 24 hour post docetaxel infusion on Day 1 of Treatment Period 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) population included all enrolled participants who received at least 2 doses of Docetaxel (75 mg/m^2) and underwent PK sampling after both doses. Here, 'Number analyzed' signifies number of participants who were evaluable for the specified category. |
| Arm/Group Title | Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg |
|---|---|
| Arm/Group Description | Docetaxel 75 mg/m^2 was administered as IV infusion for 1 hour on Day 1 in each treatment period (each treatment period was of 21 days). From Day 2 of treatment Period 1 participants received a single oral dose of Enzalutamide 160 mg once daily. Participants received a single oral dose of Dexamethasone 8 mg prior to each Docetaxel infusion and Prednisone 5 mg once daily on the days of docetaxel administration then twice daily every day thereafter as long as docetaxel treatment continued. Participants who tolerated treatment with Docetaxel and Enzalutamide received the both. |
| Measure Participants | 22 |
| Docetaxel Without Enzalutamide |
1722.1
(27.14)
|
| Docetaxel With Enzalutamide |
1662.9
(23.00)
|
| Title | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of Docetaxel With and Without Enzalutamide Treatment |
|---|---|
| Description | AUClast was observed using a linear mixed-effects model. |
| Time Frame | Docetaxel without Enzalutamide: Predose, 0.5, 1, 1.5, 2, 4, 8 and 24 hour post docetaxel infusion on Day 1 of Treatment Period 1; Docetaxel with Enzalutamide: Predose, 0.5, 1, 1.5, 2, 4, 8 and 24 hour post docetaxel infusion on Day 1 of Treatment Period 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population included all enrolled participants who received at least 2 doses of Docetaxel (75 mg/m^2) and underwent PK sampling after both doses. Here, 'Number analyzed' signifies number of participants who were evaluable for the specified category. |
| Arm/Group Title | Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg |
|---|---|
| Arm/Group Description | Docetaxel 75 mg/m^2 was administered as IV infusion for 1 hour on Day 1 in each treatment period (each treatment period was of 21 days). From Day 2 of treatment Period 1 participants received a single oral dose of Enzalutamide 160 mg once daily. Participants received a single oral dose of Dexamethasone 8 mg prior to each Docetaxel infusion and Prednisone 5 mg once daily on the days of docetaxel administration then twice daily every day thereafter as long as docetaxel treatment continued. Participants who tolerated treatment with Docetaxel and Enzalutamide received the both. |
| Measure Participants | 22 |
| Docetaxel Without Enzalutamide |
1866.6
(29.05)
|
| Docetaxel With Enzalutamide |
1674.4
(19.32)
|
| Title | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of Docetaxel With and Without Enzalutamide Treatment |
|---|---|
| Description | AUCinf was observed using a linear mixed-effects model. |
| Time Frame | Docetaxel without Enzalutamide: Predose, 0.5, 1, 1.5, 2, 4, 8 and 24 hour post docetaxel infusion on Day 1 of Treatment Period 1; Docetaxel with Enzalutamide: Predose, 0.5, 1, 1.5, 2, 4, 8 and 24 hour post docetaxel infusion on Day 1 of Treatment Period 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population included all enrolled participants who received at least 2 doses of Docetaxel (75 mg/m^2) and underwent PK sampling after both doses. Here, 'Number analyzed' signifies number of participants who were evaluable for the specified category. |
| Arm/Group Title | Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg |
|---|---|
| Arm/Group Description | Docetaxel 75 mg/m^2 was administered as IV infusion for 1 hour on Day 1 in each treatment period (each treatment period was of 21 days). From Day 2 of treatment Period 1 participants received a single oral dose of Enzalutamide 160 mg once daily. Participants received a single oral dose of Dexamethasone 8 mg prior to each Docetaxel infusion and Prednisone 5 mg once daily on the days of docetaxel administration then twice daily every day thereafter as long as docetaxel treatment continued. Participants who tolerated treatment with Docetaxel and Enzalutamide received the both. |
| Measure Participants | 22 |
| Docetaxel Without Enzalutamide |
2020.1
(27.98)
|
| Docetaxel With Enzalutamide |
1769.1
(18.91)
|
Adverse Events
| Time Frame | Baseline up to a maximum of approximately Month 12 for Combination Therapy; From Month 10.6 up to a maximum of approximately Month 71.5 for Post-Docetaxel Enzalutamide | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | An event may be categorized as serious in one participant and non-serious in another, or 1 participant may experience both event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. Safety population included all enrolled participants who received at least 1 dose or partial dose of study drug (Enzalutamide and/or Docetaxel). | |||
| Arm/Group Title | Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Post-Docetaxel Enzalutamide 160 mg | ||
| Arm/Group Description | Docetaxel 75 mg/m^2 was administered as IV infusion for 1 hour on Day 1 in each treatment period (each treatment period was of 21 days). From Day 2 of treatment Period 1 participants received a single oral dose of Enzalutamide 160 mg once daily. Participants received a single oral dose of Dexamethasone 8 mg prior to each Docetaxel infusion and Prednisone 5 mg once daily on the days of docetaxel administration then twice daily every day thereafter as long as docetaxel treatment continued. Participants who tolerated treatment with Docetaxel and Enzalutamide received the both. | Participants who had received the combination therapy of Docetaxel and Enzalutamide but discontinued the Docetaxel treatment and continued to receive a single oral dose of Enzalutamide 160 mg (4 capsule each of 40 mg) once daily up to the end of the study treatment (maximum of 70 months). | ||
All Cause Mortality |
||||
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Post-Docetaxel Enzalutamide 160 mg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Post-Docetaxel Enzalutamide 160 mg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/22 (36.4%) | 7/21 (33.3%) | ||
| Blood and lymphatic system disorders | ||||
| FEBRILE NEUTROPENIA | 3/22 (13.6%) | 0/21 (0%) | ||
| Cardiac disorders | ||||
| ACUTE CORONARY SYNDROME | 2/22 (9.1%) | 0/21 (0%) | ||
| ATRIAL FIBRILLATION | 0/22 (0%) | 3/21 (14.3%) | ||
| ATRIAL FLUTTER | 0/22 (0%) | 1/21 (4.8%) | ||
| CARDIAC FAILURE ACUTE | 0/22 (0%) | 1/21 (4.8%) | ||
| CARDIAC FAILURE CONGESTIVE | 0/22 (0%) | 1/21 (4.8%) | ||
| General disorders | ||||
| ASTHENIA | 0/22 (0%) | 1/21 (4.8%) | ||
| DEATH | 1/22 (4.5%) | 0/21 (0%) | ||
| IMPAIRED HEALING | 0/22 (0%) | 1/21 (4.8%) | ||
| PYREXIA | 1/22 (4.5%) | 1/21 (4.8%) | ||
| Hepatobiliary disorders | ||||
| Hepatic Failure | 0/22 (0%) | 1/21 (4.8%) | ||
| Infections and infestations | ||||
| CELLULITIS | 0/22 (0%) | 1/21 (4.8%) | ||
| PNEUMONIA | 0/22 (0%) | 1/21 (4.8%) | ||
| SEPSIS | 1/22 (4.5%) | 1/21 (4.8%) | ||
| SEPTIC SHOCK | 0/22 (0%) | 1/21 (4.8%) | ||
| Injury, poisoning and procedural complications | ||||
| Fall | 0/22 (0%) | 1/21 (4.8%) | ||
| Investigations | ||||
| ELECTROCARDIOGRAM QT PROLONGED | 0/22 (0%) | 1/21 (4.8%) | ||
| WHITE BLOOD CELL COUNT DECREASED | 1/22 (4.5%) | 0/21 (0%) | ||
| Metabolism and nutrition disorders | ||||
| DEHYDRATION | 0/22 (0%) | 1/21 (4.8%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| FLANK PAIN | 1/22 (4.5%) | 0/21 (0%) | ||
| Nervous system disorders | ||||
| CEREBRAL HAEMORRHAGE | 0/22 (0%) | 1/21 (4.8%) | ||
| Renal and urinary disorders | ||||
| HAEMATURIA | 1/22 (4.5%) | 0/21 (0%) | ||
| HYDRONEPHROSIS | 0/22 (0%) | 1/21 (4.8%) | ||
| OBSTRUCTIVE UROPATHY | 0/22 (0%) | 1/21 (4.8%) | ||
| RENAL FAILURE ACUTE | 0/22 (0%) | 1/21 (4.8%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| ACUTE RESPIRATORY FAILURE | 0/22 (0%) | 1/21 (4.8%) | ||
| DYSPNOEA | 0/22 (0%) | 1/21 (4.8%) | ||
| Skin and subcutaneous tissue disorders | ||||
| RASH MACULO-PAPULAR | 1/22 (4.5%) | 0/21 (0%) | ||
| Vascular disorders | ||||
| ARTERIOSCLEROSIS | 0/22 (0%) | 1/21 (4.8%) | ||
| DEEP VEIN THROMBOSIS | 0/22 (0%) | 1/21 (4.8%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Post-Docetaxel Enzalutamide 160 mg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 21/22 (95.5%) | 18/21 (85.7%) | ||
| Blood and lymphatic system disorders | ||||
| ANAEMIA | 4/22 (18.2%) | 3/21 (14.3%) | ||
| NEUTROPENIA | 19/22 (86.4%) | 1/21 (4.8%) | ||
| FEBRILE NEUTROPENIA | 1/22 (4.5%) | 0/21 (0%) | ||
| Cardiac disorders | ||||
| ANGINA PECTORIS | 0/22 (0%) | 1/21 (4.8%) | ||
| ATRIAL FIBRILLATION | 0/22 (0%) | 1/21 (4.8%) | ||
| CARDIAC FAILURE CONGESTIVE | 0/22 (0%) | 1/21 (4.8%) | ||
| Ear and labyrinth disorders | ||||
| DEAFNESS | 1/22 (4.5%) | 0/21 (0%) | ||
| TINNITUS | 0/22 (0%) | 1/21 (4.8%) | ||
| Eye disorders | ||||
| CATARACT | 0/22 (0%) | 2/21 (9.5%) | ||
| LACRIMATION INCREASED | 5/22 (22.7%) | 2/21 (9.5%) | ||
| VISION BLURRED | 2/22 (9.1%) | 1/21 (4.8%) | ||
| BLEPHAROSPASM | 1/22 (4.5%) | 0/21 (0%) | ||
| DRY EYE | 1/22 (4.5%) | 0/21 (0%) | ||
| EYE IRRITATION | 1/22 (4.5%) | 0/21 (0%) | ||
| EYE PRURITUS | 1/22 (4.5%) | 0/21 (0%) | ||
| Gastrointestinal disorders | ||||
| ABDOMINAL PAIN | 3/22 (13.6%) | 3/21 (14.3%) | ||
| CONSTIPATION | 7/22 (31.8%) | 9/21 (42.9%) | ||
| DIARRHOEA | 6/22 (27.3%) | 0/21 (0%) | ||
| DYSPEPSIA | 4/22 (18.2%) | 1/21 (4.8%) | ||
| NAUSEA | 9/22 (40.9%) | 1/21 (4.8%) | ||
| STOMATITIS | 3/22 (13.6%) | 0/21 (0%) | ||
| ABDOMINAL DISTENSION | 0/22 (0%) | 1/21 (4.8%) | ||
| ABDOMINAL PAIN LOWER | 1/22 (4.5%) | 0/21 (0%) | ||
| ABDOMINAL PAIN UPPER | 1/22 (4.5%) | 0/21 (0%) | ||
| DYSPHAGIA | 0/22 (0%) | 1/21 (4.8%) | ||
| FAECES DISCOLOURED | 1/22 (4.5%) | 0/21 (0%) | ||
| FLATULENCE | 1/22 (4.5%) | 0/21 (0%) | ||
| GASTRIC HAEMORRHAGE | 0/22 (0%) | 1/21 (4.8%) | ||
| HAEMORRHOIDAL HAEMORRHAGE | 1/22 (4.5%) | 0/21 (0%) | ||
| HAEMORRHOIDS | 1/22 (4.5%) | 0/21 (0%) | ||
| IMPAIRED GASTRIC EMPTYING | 0/22 (0%) | 1/21 (4.8%) | ||
| OESOPHAGEAL PAIN | 1/22 (4.5%) | 0/21 (0%) | ||
| OESOPHAGITIS | 0/22 (0%) | 1/21 (4.8%) | ||
| ORAL DISORDER | 0/22 (0%) | 1/21 (4.8%) | ||
| PARAESTHESIA ORAL | 1/22 (4.5%) | 0/21 (0%) | ||
| General disorders | ||||
| ASTHENIA | 3/22 (13.6%) | 1/21 (4.8%) | ||
| CHEST PAIN | 2/22 (9.1%) | 1/21 (4.8%) | ||
| FATIGUE | 16/22 (72.7%) | 5/21 (23.8%) | ||
| INFLUENZA LIKE ILLNESS | 2/22 (9.1%) | 0/21 (0%) | ||
| OEDEMA | 2/22 (9.1%) | 2/21 (9.5%) | ||
| OEDEMA PERIPHERAL | 3/22 (13.6%) | 2/21 (9.5%) | ||
| PAIN | 4/22 (18.2%) | 1/21 (4.8%) | ||
| PYREXIA | 1/22 (4.5%) | 2/21 (9.5%) | ||
| CATHETER SITE ERYTHEMA | 1/22 (4.5%) | 0/21 (0%) | ||
| CHILLS | 1/22 (4.5%) | 0/21 (0%) | ||
| GAIT DISTURBANCE | 1/22 (4.5%) | 0/21 (0%) | ||
| GENERALISED OEDEMA | 0/22 (0%) | 1/21 (4.8%) | ||
| IMPAIRED HEALING | 1/22 (4.5%) | 0/21 (0%) | ||
| MEDICAL DEVICE PAIN | 1/22 (4.5%) | 0/21 (0%) | ||
| Hepatobiliary disorders | ||||
| CHOLELITHIASIS | 1/22 (4.5%) | 0/21 (0%) | ||
| Infections and infestations | ||||
| CELLULITIS | 1/22 (4.5%) | 1/21 (4.8%) | ||
| OSTEOMYELITIS | 0/22 (0%) | 2/21 (9.5%) | ||
| RHINITIS | 1/22 (4.5%) | 1/21 (4.8%) | ||
| URINARY TRACT INFECTION | 2/22 (9.1%) | 0/21 (0%) | ||
| DEVICE RELATED INFECTION | 1/22 (4.5%) | 0/21 (0%) | ||
| FURUNCLE | 1/22 (4.5%) | 0/21 (0%) | ||
| HEPATOSPLENIC CANDIDIASIS | 0/22 (0%) | 1/21 (4.8%) | ||
| INFUSION SITE INFECTION | 1/22 (4.5%) | 0/21 (0%) | ||
| LOCALISED INFECTION | 0/22 (0%) | 1/21 (4.8%) | ||
| MUCOSAL INFECTION | 0/22 (0%) | 1/21 (4.8%) | ||
| ORAL INFECTION | 0/22 (0%) | 1/21 (4.8%) | ||
| SKIN INFECTION | 1/22 (4.5%) | 0/21 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| FALL | 1/22 (4.5%) | 0/21 (0%) | ||
| LACERATION | 0/22 (0%) | 1/21 (4.8%) | ||
| RIB FRACTURE | 0/22 (0%) | 1/21 (4.8%) | ||
| SPINAL FRACTURE | 0/22 (0%) | 1/21 (4.8%) | ||
| THERMAL BURN | 0/22 (0%) | 1/21 (4.8%) | ||
| VASCULAR ACCESS COMPLICATION | 0/22 (0%) | 1/21 (4.8%) | ||
| WOUND DEHISCENCE | 0/22 (0%) | 1/21 (4.8%) | ||
| Investigations | ||||
| BLOOD CREATININE INCREASED | 1/22 (4.5%) | 1/21 (4.8%) | ||
| BLOOD PHOSPHORUS DECREASED | 2/22 (9.1%) | 0/21 (0%) | ||
| WHITE BLOOD CELL COUNT DECREASED | 3/22 (13.6%) | 1/21 (4.8%) | ||
| BLOOD CALCIUM DECREASED | 1/22 (4.5%) | 0/21 (0%) | ||
| BLOOD CHOLESTEROL INCREASED | 0/22 (0%) | 1/21 (4.8%) | ||
| BLOOD GLUCOSE DECREASED | 1/22 (4.5%) | 0/21 (0%) | ||
| BLOOD GLUCOSE INCREASED | 0/22 (0%) | 1/21 (4.8%) | ||
| BLOOD MAGNESIUM DECREASED | 1/22 (4.5%) | 0/21 (0%) | ||
| BLOOD POTASSIUM INCREASED | 1/22 (4.5%) | 1/21 (4.8%) | ||
| BLOOD URIC ACID INCREASED | 1/22 (4.5%) | 0/21 (0%) | ||
| ELECTROCARDIOGRAM QT PROLONGED | 1/22 (4.5%) | 0/21 (0%) | ||
| WEIGHT DECREASED | 1/22 (4.5%) | 0/21 (0%) | ||
| Metabolism and nutrition disorders | ||||
| DECREASED APPETITE | 5/22 (22.7%) | 6/21 (28.6%) | ||
| DEHYDRATION | 3/22 (13.6%) | 0/21 (0%) | ||
| HYPERKALAEMIA | 0/22 (0%) | 2/21 (9.5%) | ||
| HYPOCALCAEMIA | 1/22 (4.5%) | 1/21 (4.8%) | ||
| ACIDOSIS | 0/22 (0%) | 1/21 (4.8%) | ||
| FAILURE TO THRIVE | 0/22 (0%) | 1/21 (4.8%) | ||
| HYPERCALCAEMIA | 1/22 (4.5%) | 0/21 (0%) | ||
| HYPOMAGNESAEMIA | 0/22 (0%) | 1/21 (4.8%) | ||
| METABOLIC ACIDOSIS | 0/22 (0%) | 1/21 (4.8%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| ARTHRALGIA | 6/22 (27.3%) | 4/21 (19%) | ||
| BACK PAIN | 8/22 (36.4%) | 5/21 (23.8%) | ||
| BONE PAIN | 2/22 (9.1%) | 1/21 (4.8%) | ||
| FLANK PAIN | 2/22 (9.1%) | 2/21 (9.5%) | ||
| GROIN PAIN | 1/22 (4.5%) | 2/21 (9.5%) | ||
| MUSCULOSKELETAL CHEST PAIN | 3/22 (13.6%) | 2/21 (9.5%) | ||
| MUSCULOSKELETAL DISCOMFORT | 2/22 (9.1%) | 0/21 (0%) | ||
| MUSCULOSKELETAL PAIN | 3/22 (13.6%) | 5/21 (23.8%) | ||
| NECK PAIN | 1/22 (4.5%) | 1/21 (4.8%) | ||
| PAIN IN EXTREMITY | 3/22 (13.6%) | 3/21 (14.3%) | ||
| MUSCLE SPASMS | 1/22 (4.5%) | 0/21 (0%) | ||
| MUSCULAR WEAKNESS | 0/22 (0%) | 1/21 (4.8%) | ||
| OSTEONECROSIS | 0/22 (0%) | 1/21 (4.8%) | ||
| OSTEONECROSIS OF JAW | 0/22 (0%) | 1/21 (4.8%) | ||
| PAIN IN JAW | 1/22 (4.5%) | 0/21 (0%) | ||
| Nervous system disorders | ||||
| DIZZINESS | 4/22 (18.2%) | 1/21 (4.8%) | ||
| DYSGEUSIA | 6/22 (27.3%) | 1/21 (4.8%) | ||
| HEADACHE | 3/22 (13.6%) | 0/21 (0%) | ||
| NEUROPATHY PERIPHERAL | 10/22 (45.5%) | 1/21 (4.8%) | ||
| PERIPHERAL MOTOR NEUROPATHY | 3/22 (13.6%) | 1/21 (4.8%) | ||
| PERIPHERAL SENSORY NEUROPATHY | 7/22 (31.8%) | 4/21 (19%) | ||
| AMNESIA | 1/22 (4.5%) | 0/21 (0%) | ||
| APHASIA | 0/22 (0%) | 1/21 (4.8%) | ||
| BALANCE DISORDER | 1/22 (4.5%) | 0/21 (0%) | ||
| COGNITIVE DISORDER | 0/22 (0%) | 1/21 (4.8%) | ||
| HYPOKINESIA | 0/22 (0%) | 1/21 (4.8%) | ||
| PARAESTHESIA | 0/22 (0%) | 1/21 (4.8%) | ||
| Psychiatric disorders | ||||
| DEPRESSION | 0/22 (0%) | 2/21 (9.5%) | ||
| INSOMNIA | 4/22 (18.2%) | 1/21 (4.8%) | ||
| AGITATION | 0/22 (0%) | 1/21 (4.8%) | ||
| Renal and urinary disorders | ||||
| HAEMORRHAGE URINARY TRACT | 2/22 (9.1%) | 2/21 (9.5%) | ||
| INCONTINENCE | 1/22 (4.5%) | 1/21 (4.8%) | ||
| POLLAKIURIA | 3/22 (13.6%) | 3/21 (14.3%) | ||
| URETHRAL PAIN | 0/22 (0%) | 2/21 (9.5%) | ||
| BLADDER SPASM | 0/22 (0%) | 1/21 (4.8%) | ||
| HAEMATURIA | 0/22 (0%) | 1/21 (4.8%) | ||
| URINARY INCONTINENCE | 0/22 (0%) | 1/21 (4.8%) | ||
| Reproductive system and breast disorders | ||||
| PELVIC PAIN | 0/22 (0%) | 2/21 (9.5%) | ||
| NIPPLE DISORDER | 0/22 (0%) | 1/21 (4.8%) | ||
| SCROTAL OEDEMA | 1/22 (4.5%) | 0/21 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| COUGH | 1/22 (4.5%) | 1/21 (4.8%) | ||
| DYSPNOEA | 6/22 (27.3%) | 4/21 (19%) | ||
| DYSPNOEA EXERTIONAL | 4/22 (18.2%) | 0/21 (0%) | ||
| EPISTAXIS | 1/22 (4.5%) | 0/21 (0%) | ||
| PLEURAL EFFUSION | 0/22 (0%) | 1/21 (4.8%) | ||
| PRODUCTIVE COUGH | 0/22 (0%) | 1/21 (4.8%) | ||
| RHINITIS ALLERGIC | 0/22 (0%) | 1/21 (4.8%) | ||
| Skin and subcutaneous tissue disorders | ||||
| ALOPECIA | 6/22 (27.3%) | 0/21 (0%) | ||
| DRY SKIN | 1/22 (4.5%) | 1/21 (4.8%) | ||
| NAIL DISORDER | 3/22 (13.6%) | 1/21 (4.8%) | ||
| RASH | 3/22 (13.6%) | 3/21 (14.3%) | ||
| NAIL DISCOLOURATION | 1/22 (4.5%) | 0/21 (0%) | ||
| ONYCHOMADESIS | 1/22 (4.5%) | 0/21 (0%) | ||
| PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME | 1/22 (4.5%) | 0/21 (0%) | ||
| SKIN ULCER | 0/22 (0%) | 1/21 (4.8%) | ||
| Vascular disorders | ||||
| HOT FLUSH | 1/22 (4.5%) | 2/21 (9.5%) | ||
| HYPERTENSION | 1/22 (4.5%) | 1/21 (4.8%) | ||
| HYPOTENSION | 1/22 (4.5%) | 1/21 (4.8%) | ||
| INTERMITTENT CLAUDICATION | 2/22 (9.1%) | 1/21 (4.8%) | ||
| ARTERIOSCLEROSIS | 0/22 (0%) | 1/21 (4.8%) | ||
| FLUSHING | 1/22 (4.5%) | 0/21 (0%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01565928
Other Study ID Numbers:
- MDV3100-06
- C3431002
First Posted:
Mar 29, 2012
Last Update Posted:
Apr 22, 2019
Last Verified:
Jan 1, 2019