Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Hormones

MDV3100 daily until progression or dose-limiting toxicity

MDV3100

Pfizer Pfizer CT.gov Call Center

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.

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.

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

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

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.

Prostate-specific antigen is a glycoprotein considered as a biomarker for the response to therapy in men with prostate cancer. A 50 percent (%) decline in PSA from baseline to the PSA level at Day 84 was considered as a PSA response.

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.

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.

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.

T 1/2 is the time measured for the plasma concentration of MDV3100 to decrease by one half.

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.

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.

Astellas Pharma Inc

Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

Pfizer

Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or participant may have experienced both SAE and NSAE. Analysis population included all enrolled participants who received at least 1 dose of study drug.

Participants received 30 mg of Enzalutamide on Day 1 and were followed for 6 days in single dose period and continued to receive the same dose in multiple dose period for 84 days.

MDV3100 (Enzalutamide) 30 mg/Day

Participants received 60 mg of Enzalutamide on Day 1 and were followed for 6 days in single dose period and continued to receive the same dose in multiple dose period for 84 days.

MDV3100 (Enzalutamide) 60 mg /Day

Participants who received 150 mg of Enzalutamide on Day 1 and were followed for 6 days in single dose period. This dose was then changed subsequently to 160 mg/day according to Protocol amendment. Participants continued to receive the same dose in multiple dose period for 84 days.

MDV3100 (Enzalutamide) 150/160 mg/Day

Participants received 240 mg of Enzalutamide on Day 1 and were followed for 6 days in single dose period and continued to receive the same dose in multiple dose period for 84 days.

MDV3100 (Enzalutamide) 240 mg /Day

Participants received 360 mg of Enzalutamide on Day 1 and were followed for 6 days in single dose period and continued to receive the same dose in multiple dose period for 84 days.

MDV3100 (Enzalutamide) 360 mg /Day

Participants received 480 mg of Enzalutamide on Day 1 and were followed for 6 days in single dose period and continued to receive the same dose in multiple dose period for 84 days.

MDV3100 (Enzalutamide) 480 mg /Day

Participants received 600 mg of Enzalutamide on Day 1 and were followed for 6 days in single dose period and continued to receive the same dose in multiple dose period for 84 days.

MDV3100 (Enzalutamide) 600 mg /Day

All participants after multiple dose period, continued to receive 160 mg/day oral dose of Enzalutamide in long term dosing period until they voluntarily withdrew, experienced a DLT or were diagnosed with disease progression.

MDV3100 (Enzalutamide) 160 mg /Day: Long Term Dosing Period

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Safety population included all enrolled participants who received at least 1 dose of study drug.

Pfizer ClinicalTrials.gov Call Center

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)

Percentage of Participants With at Least 1 Dose-limiting Toxicity (DLT): Multiple Dose Period

Participants received single oral dose of MDV3100 in 1 out of the 7 cohorts of 30, 60, 150, 240, 360, 480 or 600 mg/day dose on Day 1 and were followed up for 6 days in single dose (dose escalation) period. Dose escalation from 30 to 600 mg/day continued until the MTD was determined or until a dose of 600 mg/day was evaluated. After dose-escalation, the cohorts receiving 60-600 mg/day dose were expanded in multiple dose (dose expansion) period, where participants received MDV3100 according to their dose in single dose period for 84 days.

MDV3100 (Enzalutamide) : All Participants

Maximum Tolerated Dose (MTD) of MDV3100: Multiple Dose Period

Pharmacokinetic (PK) evaluable population: all participants who received study drug and had sufficient PK samples for calculation of at least 1 MDV3100 PK parameter. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure.

Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Single Dose Period

PK evaluable population: all participants who received study drug and had sufficient PK samples for calculation of at least 1 MDV3100 PK parameter. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure.

Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of MDV3100: Single Dose Period

Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of MDV3100: Single Dose Period

PK evaluable population: all participants who received study drug and had sufficient PK samples for calculation of at least 1 MDV3100 PK parameter.

Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Single Dose Period

Maximum Plasma Concentration (Cmax) of MDV3100: Single Dose Period

Apparent Terminal Elimination Half-Life (T1/2) of MDV3100: Single Dose Period

Apparent Volume of Distribution (V/F) of MDV3100: Single Dose Period

Apparent Total Plasma Clearance (CL/F) of MDV3100: 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

Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Multiple Dose Period

Maximum Plasma Concentration (Cmax) of MDV3100: Multiple Dose Period

Minimum Observed Plasma Concentration (Cmin) of MDV3100: Multiple Dose Period

Apparent Total Plasma Clearance (CL/F) of MDV3100: Multiple Dose Period

Analysis population included all enrolled participants who received at least 1 dose of study drug. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Percentage of Participants With Prostate Specific Antigen (PSA) Response at Day 84: Multiple Dose Period

Participants with no prior exposure to chemotherapy received single oral dose of MDV3100 in 1 out of the 7 cohorts of 30, 60, 150, 240, 360, 480 or 600 milligram per day (mg/day) dose on Day 1 and were followed up for 6 days in single dose (dose escalation) period. Dose escalation from 30 to 600 mg/day continued until the maximum tolerated dose (MTD) was determined or until a dose of 600 mg/day was evaluated. After dose-escalation, the cohorts receiving 60-600 mg/day dose were expanded in multiple dose (dose expansion) period, where participants received MDV3100 according to their dose in single dose period for 84 days. This was followed by long-term dosing period in which participants continued to receive 160 mg/day dose of MDV3100 until withdrew of consent, dose limiting toxicity (DLT) or disease progression occurred. Participants were followed up for 30 days after last dose of study drug for safety follow up.

MDV3100 (Enzalutamide): No Previous Chemotherapy

Participants with prior exposure to chemotherapy single oral dose of MDV3100 in 1 out of the 7 cohorts of 30, 60, 150, 240, 360, 480 or 600 mg/day dose on Day 1 and were followed up for 6 days in single dose (dose escalation) period. Dose escalation from 30 to 600 mg/day continued until the MTD was determined or until a dose of 600 mg/day was evaluated. After dose-escalation, the cohorts receiving 60-600 mg/day dose were expanded in multiple dose (dose expansion) period, where participants received MDV3100 according to their dose in single dose period, for 84 days. This was followed by long-term dosing period in which participants continued to receive 160 mg/day dose of MDV3100 until withdrew of consent, DLT or disease progression occurred. Participants were followed up for 30 days after last dose.

Spots Global Cancer Trial Database for A Phase 1 Study of MDV3100 in Patients With Castration-Resistant (Hormone-Refractory) Prostate Cancer

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Study Description

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