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

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

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

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: MDV3100

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MDV3100	Drug: MDV3100; 4 x 40 mg capsules, orally, once per day

What is the study measuring?

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
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
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	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

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Astellas Pharma Inc; Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): February 26, 2018

Study Registration Dates

• First Submitted: February 8, 2012
• First Submitted That Met QC Criteria: March 27, 2012
• First Posted (Estimate): March 29, 2012

Study Record Updates

• Last Update Posted (Actual): April 22, 2019
• Last Update Submitted That Met QC Criteria: January 25, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Prostate cancer; Xtandi; MDV3100; enzalutamide; docetaxel
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: MDV3100-06; C3431002 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.