Clinical trial NCT00510718: A Phase 1 Study of MDV3100 in Patients With Castration-Resistant (Hormone-Refractory) Prostate Cancer
Official title: A PHASE 1, OPEN-LABEL, DOSE-ESCALATION SAFETY AND PHARMACOKINETIC STUDY OF MDV3100 IN PATIENTS WITH CASTRATION-RESISTANT PROSTATE CANCER
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostate Cancer
Hormone Refractory Prostate Cancer
Keywords: Prostate
Cancer
Hormone
Refractory
Castration
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Astellas Pharma Inc
name: Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
First posted: 2007-08-02
Enrollment: 140
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Histologically or cytologically confirmed adenocarcinoma of the prostate;
2. Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration);
3. 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);

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
timeFrame: Baseline up to 30 days after last dose of study treatment (approximately maximum of 129 months)
measure: Percentage of Participants With at Least 1 Dose-limiting Toxicity (DLT): Multiple Dose Period
timeFrame: Baseline up to first 35 days of the study treatment in multiple dose period
measure: Maximum Tolerated Dose (MTD) of MDV3100: Multiple Dose Period
timeFrame: Baseline up to first 35 days of the study treatment in multiple dose period
Secondary outcomes:
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
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, 24 hours post dose on Day 1 of Single Dose Period
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
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours postdose on Day 1 of Single Dose Period
measure: Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of MDV3100: Single Dose Period
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period
measure: Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Single Dose Period
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period
measure: Maximum Plasma Concentration (Cmax) of MDV3100: Single Dose Period
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period
measure: Apparent Terminal Elimination Half-Life (T1/2) of MDV3100: Single Dose Period
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period
measure: Apparent Volume of Distribution (V/F) of MDV3100: Single Dose Period
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period
measure: Apparent Total Plasma Clearance (CL/F) of MDV3100: Single Dose Period
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period
measure: Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Multiple Dose Period
timeFrame: Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period
measure: Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Multiple Dose Period
timeFrame: Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period
measure: Maximum Plasma Concentration (Cmax) of MDV3100: Multiple Dose Period
timeFrame: Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period
measure: Minimum Observed Plasma Concentration (Cmin) of MDV3100: Multiple Dose Period
timeFrame: Pre-dose on Day 1 of Multiple Dose Period
measure: Apparent Total Plasma Clearance (CL/F) of MDV3100: Multiple Dose Period
timeFrame: Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period
Other outcomes:
measure: Percentage of Participants With Prostate Specific Antigen (PSA) Response at Day 84: Multiple Dose Period
timeFrame: Baseline, Day 84
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute (DFCI)
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center (BIDMC)
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: MSKCC- Sidney Kimmel Center
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Houston
country: United States
facility: Investigational Pharmacy Services
state: Texas
city: Houston
country: United States
facility: The University of Texas M.D. Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: Pfizer
name: Pfizer Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Gibbons JA, Ouatas T, Krauwinkel W, Ohtsu Y, van der Walt JS, Beddo V, de Vries M, Mordenti J. Clinical Pharmacokinetic Studies of Enzalutamide. Clin Pharmacokinet. 2015 Oct;54(10):1043-55. doi: 10.1007/s40262-015-0271-5.
citation: Scher HI, Beer TM, Higano CS, Anand A, Taplin ME, Efstathiou E, Rathkopf D, Shelkey J, Yu EY, Alumkal J, Hung D, Hirmand M, Seely L, Morris MJ, Danila DC, Humm J, Larson S, Fleisher M, Sawyers CL; Prostate Cancer Foundation/Department of Defense Prostate Cancer Clinical Trials Consortium. Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study. Lancet. 2010 Apr 24;375(9724):1437-46. doi: 10.1016/S0140-6736(10)60172-9. Epub 2010 Apr 14.