Safety and Tolerability Study of MDV3100 in Combination With Docetaxel in Men With Advanced Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety of MDV3100 given in combination with Docetaxel in men with advanced prostate cancer.

Official Title
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A PHASE 1B, OPEN-LABEL, SAFETY AND TOLERABILITY STUDY OF ORAL MDV3100 IN COMBINATION WITH DOCETAXEL IN MEN WITH ADVANCED PROSTATE CANCER

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: MDV3100


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MDV3100<br> | Drug: MDV3100<br>* 4 x 40 mg capsules, orally, once per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Treatment Period 1 (Day 1) up to end of Treatment Period 2 (42 days) | 
| 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. | Treatment Period 1 (Day 1) up to end of study treatment (maximum 70 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 Extrapolated to Infinite Time (AUCinf) of Docetaxel With and Without Enzalutamide Treatment | AUCinf was observed using a linear mixed-effects model. | 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 | 
| 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 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. | 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 | 
| 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. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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docetaxel, Prostate cancer, MDV3100, enzalutamide, Xtandi