A Phase 1 Study of MDV3100 in Patients With Castration-Resistant (Hormone-Refractory) Prostate Cancer
- Conditions
- Hormone Refractory Prostate CancerProstate Cancer
- Interventions
- Drug: MDV3100
- Registration Number
- NCT00510718
- Lead Sponsor
- Pfizer
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 140
- 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,
- Metastases in the brain or active epidural disease. (Note: patients with treated epidural disease are allowed);
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description 1 MDV3100 MDV3100
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) Baseline up to 30 days after last dose of study treatment (approximately maximum of 129 months) 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.
Percentage of Participants With at Least 1 Dose-limiting Toxicity (DLT): Multiple Dose Period Baseline up to first 35 days of the study treatment in 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.
Maximum Tolerated Dose (MTD) of MDV3100: Multiple Dose Period Baseline up to first 35 days of the study treatment in 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.
- Secondary Outcome Measures
Name Time Method 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 Apparent Volume of Distribution (V/F) 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 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.
Apparent Total Plasma Clearance (CL/F) 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 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.
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 Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period T 1/2 is the time measured for the plasma concentration of MDV3100 to decrease by one half.
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 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 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 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 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 Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of 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.
Trial Locations
- Locations (9)
Beth Israel Deaconess Medical Center (BIDMC)
🇺🇸Boston, Massachusetts, United States
Investigational Pharmacy Services
🇺🇸Houston, Texas, United States
The University of Texas M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Dana-Farber Cancer Institute (DFCI)
🇺🇸Boston, Massachusetts, United States
MSKCC- Sidney Kimmel Center
🇺🇸New York, New York, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States