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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00510718
• Other study ID #: S-3100-1-01
• Secondary ID: C3431009
• Status: Completed
• Phase: Phase 1
• Start date: July 23, 2007
• Est. completion date: April 2, 2018

Study information

• Verified date: September 2019
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00513812

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: April 2, 2018
• Est. primary completion date: December 8, 2008
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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);

Related Conditions & MeSH terms

• Hormone Refractory Prostate Cancer
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• MDV3100
MDV3100 daily until progression or dose-limiting toxicity

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center (BIDMC)	Boston	Massachusetts
United States	Dana-Farber Cancer Institute (DFCI)	Boston	Massachusetts
United States	Investigational Pharmacy Services	Houston	Texas
United States	The University of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	MSKCC- Sidney Kimmel Center	New York	New York
United States	Oregon Health & Science University	Portland	Oregon
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Pfizer	Astellas Pharma Inc, Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants With Prostate Specific Antigen (PSA) Response at Day 84: Multiple Dose Period	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.	Baseline, Day 84
Primary	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)
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Minimum Observed Plasma Concentration (Cmin) of MDV3100: Multiple Dose Period		Pre-dose on Day 1 of Multiple Dose Period
Secondary	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