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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

MDV3100

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring Prostate, Cancer, Hormone, Refractory, Castration

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

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);

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

MDV3100

Outcomes

Primary Outcome Measures

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.

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.

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.

Secondary Outcome Measures

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

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

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

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

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.

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.

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

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.

Full Information

NCT ID

NCT00510718

First Posted

July 31, 2007

Last Updated

September 10, 2019

Sponsor

Pfizer

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT00510718

Brief Title

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

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Completed

Study Start Date

July 23, 2007 (Actual)

Primary Completion Date

December 8, 2008 (Actual)

Study Completion Date

April 2, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

Collaborators

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

4. Oversight

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer, Hormone Refractory Prostate Cancer

Keywords

Prostate, Cancer, Hormone, Refractory, Castration

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Masking

None (Open Label)

Enrollment

140 (Actual)

8. Arms, Groups, and Interventions

Arm Title

1

Arm Type

Experimental

Arm Description

MDV3100

Intervention Type

Drug

Intervention Name(s)

MDV3100

Other Intervention Name(s)

enzalutamide, Xtandi

Intervention Description

MDV3100 daily until progression or dose-limiting toxicity

Primary Outcome Measure Information:

Title

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

Description

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.

Time Frame

Baseline up to 30 days after last dose of study treatment (approximately maximum of 129 months)

Title

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

Description

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.

Time Frame

Baseline up to first 35 days of the study treatment in multiple dose period

Title

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

Description

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.

Time Frame

Baseline up to first 35 days of the study treatment in multiple dose period

Secondary Outcome Measure Information:

Title

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

Time Frame

Pre-dose, 0.5, 1, 2, 4, 6, 24 hours post dose on Day 1 of Single Dose Period

Title

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

Time Frame

Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours postdose on Day 1 of Single Dose Period

Title

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

Time Frame