Prostate Cancer
Conditions
Keywords
Prostate cancer, docetaxel, MDV3100, enzalutamide, Xtandi
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.
Interventions
DRUGMDV3100
4 x 40 mg capsules, orally, once per day
Sponsors
Astellas Pharma Inc
Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel 75 mg/m^2+ Enzalutamide 160 mg 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). | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Death | 2 |
| Overall Study | Other | 3 |
| Overall Study | Progressive Disease | 13 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Docetaxel 75 mg/m^2+ Enzalutamide 160 mg |
|---|---|
| Age, Continuous | 68.0 years STANDARD_DEVIATION 10.66 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 22 | 18 / 21 |
| serious Total, serious adverse events | 8 / 22 | 7 / 21 |
Outcome results
Primary
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)
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)
Population: Safety population included all enrolled participants who received at least 1 dose or partial dose of study drug (Enzalutamide and/or Docetaxel).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 9.1 percentage of participants |
Primary
Percentage of Participants Who Required Study Drug Dose Reduction During Treatment Periods 1 and 2
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)
Population: Safety population included all enrolled participants who received at least 1 dose or partial dose of study drug (Enzalutamide and/or Docetaxel).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Percentage of Participants Who Required Study Drug Dose Reduction During Treatment Periods 1 and 2 | Docetaxel Dose Reductions | 4.5 percentage of participants |
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Percentage of Participants Who Required Study Drug Dose Reduction During Treatment Periods 1 and 2 | Enzalutamide Dose Reductions | 0.0 percentage of participants |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of Docetaxel With and Without Enzalutamide Treatment
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | 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 | 2020.1 nanograms*hour per milliliter | Geometric Coefficient of Variation 27.98 |
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of Docetaxel With and Without Enzalutamide Treatment | Docetaxel With Enzalutamide | 1769.1 nanograms*hour per milliliter | Geometric Coefficient of Variation 18.91 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of Docetaxel With and Without Enzalutamide Treatment
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | 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 | 1866.6 nanograms*hour per milliliter | Geometric Coefficient of Variation 29.05 |
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of Docetaxel With and Without Enzalutamide Treatment | Docetaxel With Enzalutamide | 1674.4 nanograms*hour per milliliter | Geometric Coefficient of Variation 19.32 |
Secondary
Maximum Plasma Concentration (Cmax) of Docetaxel With and Without Enzalutamide Treatment
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Maximum Plasma Concentration (Cmax) of Docetaxel With and Without Enzalutamide Treatment | Docetaxel Without Enzalutamide | 1722.1 nanograms per milliliter | Geometric Coefficient of Variation 27.14 |
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Maximum Plasma Concentration (Cmax) of Docetaxel With and Without Enzalutamide Treatment | Docetaxel With Enzalutamide | 1662.9 nanograms per milliliter | Geometric Coefficient of Variation 23 |
Secondary
Number of Participants With Clinically Significant Abnormalities in Vital Signs
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
Population: Safety population included all enrolled participants who received at least 1 dose or partial dose of study drug (Enzalutamide and/or Docetaxel).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | SBP: AR- < 90 mmHg, decrease from BL > 30 mmHg | 1 Participants |
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | DBP: Most extreme post-BL result >= 90 mmHg | 3 Participants |
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | SBP: Most extreme post- BL result >= 180 mmHg | 0 Participants |
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | DBP: Most extreme post-BL result >= 105 mmHg | 0 Participants |
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | SBP: AR- > 180 mmHg, increase from BL > 40 mmHg | 0 Participants |
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | DBP: MER >= 105 mmHg,>= 15 mmHg change from BL | 0 Participants |
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | SBP: MER >= 180 mmHg, >= 20 mmHg change from BL | 0 Participants |
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | DBP: MER >= 90 mmHg,>= 15 mmHg change from BL | 1 Participants |
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | SBP: Most extreme post- BL result >= 140 mmHg | 10 Participants |
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | Heart Rate: AR >120 bpm, increase from BL >30 bpm | 0 Participants |
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | SBP: MER >= 140 mmHg, >= 20 mmHg change from BL | 5 Participants |
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | Heart Rate: AR <50 bpm, decrease from BL >30 bpm | 0 Participants |
| Post-Docetaxel Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | SBP: MER >= 140 mmHg, >= 20 mmHg change from BL | 5 Participants |
| Post-Docetaxel Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | SBP: AR- > 180 mmHg, increase from BL > 40 mmHg | 1 Participants |
| Post-Docetaxel Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | SBP: AR- < 90 mmHg, decrease from BL > 30 mmHg | 0 Participants |
| Post-Docetaxel Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | SBP: Most extreme post- BL result >= 140 mmHg | 7 Participants |
| Post-Docetaxel Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | SBP: Most extreme post- BL result >= 180 mmHg | 2 Participants |
| Post-Docetaxel Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | SBP: MER >= 180 mmHg, >= 20 mmHg change from BL | 2 Participants |
| Post-Docetaxel Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | Heart Rate: AR <50 bpm, decrease from BL >30 bpm | 1 Participants |
| Post-Docetaxel Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | DBP: Most extreme post-BL result >= 90 mmHg | 6 Participants |
| Post-Docetaxel Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | DBP: Most extreme post-BL result >= 105 mmHg | 1 Participants |
| Post-Docetaxel Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | DBP: MER >= 105 mmHg,>= 15 mmHg change from BL | 1 Participants |
| Post-Docetaxel Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | DBP: MER >= 90 mmHg,>= 15 mmHg change from BL | 4 Participants |
| Post-Docetaxel Enzalutamide 160 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | Heart Rate: AR >120 bpm, increase from BL >30 bpm | 1 Participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Electrocardiograms (ECG)
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
Population: Safety population included all enrolled participants who received at least 1 dose or partial dose of study drug (Enzalutamide and/or Docetaxel).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg | Number of Participants With Clinically Significant Change From Baseline in Electrocardiograms (ECG) | 1 Participants |
| Post-Docetaxel Enzalutamide 160 mg | Number of Participants With Clinically Significant Change From Baseline in Electrocardiograms (ECG) | 0 Participants |