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

NCT00510718 | Completed Phase 1 Results

• 2 other identifiers: S-3100-1-01C3431009
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 9

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.

Conditions

Prostate Cancer; Hormone Refractory Prostate Cancer

Keywords

Prostate; Cancer; Hormone; Refractory; Castration

Outcome Measures

Primary Outcomes (3)

• 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)

• 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

• 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 Outcomes (13)

• 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

• 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 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

• 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

• 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

Other Outcomes (1)

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

  Baseline, Day 84

Study Arms (1)

1

EXPERIMENTAL

MDV3100

Drug: MDV3100

Interventions

MDV3100 DRUG

MDV3100 daily until progression or dose-limiting toxicity

Also known as: enzalutamide, Xtandi

1

Eligibility Criteria

• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,

You may not qualify if:

• \. Metastases in the brain or active epidural disease. (Note: patients with treated epidural disease are allowed);

Sponsors & Collaborators

• Pfizer: lead
• Astellas Pharma Inc: collaborator
• Medivation LLC, a wholly owned subsidiary of Pfizer Inc.: collaborator

Study Sites (9)

Dana-Farber Cancer Institute (DFCI)

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center (BIDMC)

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

MSKCC- Sidney Kimmel Center

New York, New York, 10065, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Investigational Pharmacy Services

Houston, Texas, 77030-4009, United States

Location

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Related Publications (2)

• 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.

  PMID: 25917876 DERIVED

• 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.

  PMID: 20398925 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasms

Interventions

enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2007
• First Posted: August 2, 2007
• Study Start: July 23, 2007
• Primary Completion: December 8, 2008
• Study Completion: April 2, 2018
• Last Updated: October 3, 2019
• Results First Posted: October 3, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)