A Phase 1 Study of MDV3100 in Patients With Castration-Resistant (Hormone-Refractory) Prostate Cancer

Study Overview
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Brief Summary
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This is a multi-center open-label dose-escalation study of a novel compound (MDV3100) to treat patients with castration-resistant (hormone-refractory) prostate cancer. Additional patients will be enrolled in expanded cohorts at doses determined to be tolerable. Patients who tolerate the drug and do not progress will be allowed to continue to look for PSA response.

Detailed Description
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This is a Phase 1, open-label, uncontrolled, dose-escalation study with dose-expansion at doses determined to be tolerated. Patients who tolerate the drug and do not progress will be allowed to continue treatment. The study endpoints are safety and tolerability and pharmacokinetics. PSA values will also be collected to look for PSA response.

Official Title
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A PHASE 1, OPEN-LABEL, DOSE-ESCALATION SAFETY AND PHARMACOKINETIC STUDY OF MDV3100 IN PATIENTS WITH CASTRATION-RESISTANT PROSTATE CANCER

Conditions
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Prostate Cancer, Hormone Refractory Prostate Cancer

Intervention / Treatment
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* Drug: MDV3100


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the prostate; Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration); Progressive disease after medical or surgical castration, Exclusion Criteria: 1. Metastases in the brain or active epidural disease. (Note: patients with treated epidural disease are allowed);
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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>MDV3100 | Drug: MDV3100<br>* MDV3100 daily until progression or dose-limiting toxicity<br>* Other names: Xtandi;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | An adverse events (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both SAEs and non-SAEs. | Baseline up to 30 days after last dose of study treatment (approximately maximum of 129 months) | 
| Percentage of Participants With at Least 1 Dose-limiting Toxicity (DLT): Multiple Dose Period | DLT was defined as a national cancer institute's common toxicity criteria for adverse events (NCI-CTCAE) version 3.0 grade 3 or greater toxicity regardless of perceived causality that is not improved by the use of adequate/maximal medical intervention. Grade 3 alopecia, fever without neutropenia, nausea, vomiting, fatigue, and self-limited or medically controllable adverse events were not considered as DLTs. | Baseline up to first 35 days of the study treatment in multiple dose period | 
| Maximum Tolerated Dose (MTD) of MDV3100: Multiple Dose Period | Tolerability was defined as if less than (<) 4/12 in participants with no prior exposure to MDV3100 (chemo-naive) and < 4/12 prior chemotherapy participants experienced a DLT within the first 35 days of the multiple dose period. For doses higher than 360 mg/day, tolerability was defined if <8/24 participants previously treated with chemotherapy experience a DLT within the first 35 days of the multiple dose period. MTD was defined as a dose below the intolerable dose. | Baseline up to first 35 days of the study treatment in multiple dose period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Single Dose Period |  | Pre-dose, 0.5, 1, 2, 4, 6, 24 hours post dose on Day 1 of Single Dose Period | 
| Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of MDV3100: Single Dose Period |  | Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours postdose on Day 1 of Single Dose Period | 
| Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of MDV3100: Single Dose Period |  | Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period | 
| Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Single Dose Period |  | Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period | 
| Maximum Plasma Concentration (Cmax) of MDV3100: Single Dose Period |  | Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period | 
| Apparent Terminal Elimination Half-Life (T1/2) of MDV3100: Single Dose Period | T 1/2 is the time measured for the plasma concentration of MDV3100 to decrease by one half. | Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period | 
| Apparent Volume of Distribution (V/F) of MDV3100: Single Dose Period | Volume of distribution is defined as the theoretical volume in which the total amount of MDV3100 would need to be uniformly distributed to produce the desired plasma concentration of MDV3100. Apparent volume of distribution after oral dose (V/F) is influenced by the fraction absorbed. | Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period | 
| Apparent Total Plasma Clearance (CL/F) of MDV3100: Single Dose Period | Clearance of a MDV3100 is a measure of the rate at which a MDV3100 is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. | Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period | 
| Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Multiple Dose Period |  | Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period | 
| Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Multiple Dose Period |  | Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period | 
| Maximum Plasma Concentration (Cmax) of MDV3100: Multiple Dose Period |  | Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period | 
| Minimum Observed Plasma Concentration (Cmin) of MDV3100: Multiple Dose Period |  | Pre-dose on Day 1 of Multiple Dose Period | 
| Apparent Total Plasma Clearance (CL/F) of MDV3100: Multiple Dose Period | Clearance of a MDV3100 is a measure of the rate at which a MDV3100 is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. | Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate, Cancer, Hormone, Refractory, Castration