A Study of Enzalutamide Re-treatment in Metastatic Castration-resistant Prostate Cancer After Docetaxel and/or Cabazitaxel Treatment

NCT02441517 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: 9785-MA-1008
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of the study was to understand if there is benefit in treatment with a medicine called enzalutamide in the re-treatment setting. Patients must have been previously treated with enzalutamide in the pre-chemotherapy setting for a minimum of 8 months and have disease progressed, followed by docetaxel and/or cabazitaxel for at least 4 cycles.

Conditions

Metastatic Castration Resistant Prostate Cancer

Keywords

Xtandi; Metastatic Castration Resistant Prostate Cancer; Metastatic; Prostate Cancer; Chemotherapy; Castration-resistant; Enzalutamide

Outcome Measures

Primary Outcomes (1)

• Radiographic Progression Free Survival (rPFS)

  Radiographic PFS (rPFS) was defined as the time from first dose to the radiographic disease progression (PD), or death on study, whichever occurred first. Radiological PD was defined by either soft tissue tumor progression defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, or bone progression defined by the Prostate Cancer Clinical Trials Working Group 2 (PCWG2). Bone progression per PCWG2 was defined as a minimum of two new lesions. Progression on bone scans at time points before or at week 9 required a confirmatory scan performed six or more weeks later, where it should have demonstrated at least 2 additional new lesions (PCWG2) compared to the week 9 scan. rPFS was analyzed using Kaplan-Meier methodology to account for censored outcomes (i.e., no observation of rPFS event within the study follow-up period).

  From first dose of study drug up to date of last evaluation of 15 March 2017 (approximately 17 months)

Secondary Outcomes (6)

• Overall Survival

  From first dose of study drug up to date of last evaluation of 15 March 2017 (approximately 17 months)

• Time to Prostate-Specific Antigen (PSA) Progression

  From first dose of study drug up to date of last evaluation of 15 March 2017 (approximately 17 months)

• Number of Participants With PSA Response

  From baseline up to date of last evaluation of 15 March 2017 (approximately 17 months)

• Number of Participants With Objective Response

  From first dose of study drug up to date of last evaluation of 15 March 2017 (approximately 17 months)

• Time to First Use of a Subsequent Antineoplastic Therapy

  From first dose of study drug up to date of last evaluation of 15 March 2017 (approximately 17 months)

Study Arms (1)

Enzalutamide

EXPERIMENTAL

Participants received 160 mg enzalutamide orally once daily until radiographic or clinical progression, or unacceptable toxicity.

Drug: Enzalutamide

Interventions

Enzalutamide DRUG

Participants were administered four 40-mg capsules orally once daily and taken as close to the same time each day as possible and could be taken with or without food.

Also known as: ASP9785, Xtandi, MDV3100

Enzalutamide

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of the prostate without signet ring cell features.
• Presence of metastatic disease (M1) as assessed by computed tomography/ magnetic resonance imaging (CT/MRI) and/or whole-body radionuclide bone scan.
• Subject has been previously treated with enzalutamide for at least 8 months, and stopped enzalutamide due to progressive disease (not due to adverse events), followed by at least 4 cycles of docetaxel and/or cabazitaxel chemotherapy, with or without other intervening anti-cancer therapies (including but not limited to aminoglutethimide, ketoconozole, abiraterone acetate, Rad-223, or sipuleucel-T), prior to receiving chemotherapy. Note: for patients who receive sequential taxanes, there must not have been progressive disease upon ending the first taxane, or use of any anti-cancer agents between the two taxanes.
• Ongoing androgen deprivation therapy with an gonadotropin releasing hormone (GnRH) analogue or prior bilateral orchiectomy (medical or surgical castration). For patients who have not had bilateral orchiectomy, there must be a plan to maintain effective GnRH-analogue for the duration of the trial.
• Testosterone ≤ 1.73 nmol/L (≤ 50 ng/dL) at screening.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at screening.
• Estimated life expectancy of ≥ 6 months at screening.
• Ability to swallow study drugs and to comply with study requirements throughout the study.
• Throughout study, male subject and a female partner who is of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration. Two acceptable methods of birth control thus include the following:
• Condom (barrier method of contraception) AND
• One of the following is required:
• Established use of oral, injected, or implanted hormonal method of contraception by the female partner performed at least 6 months before screening;
• Placement of an intrauterine device or intrauterine system by the female partner;
• Additional barrier method: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository by the female partner;
• Tubal ligation in the female partner.

You may not qualify if:

• Known or suspected neuroendocrine/small cell feature.
• Use of any antineoplastic treatment post-chemotherapy, including but not limited to aminoglutethimide, ketoconozole, abiraterone acetate, Rad-223, sipuleucel-T, or enzalutamide. Continuing steroids is permitted.
• Palliative radiation therapy within 2 weeks of Day 1, or within 4 weeks of Day 1 if a radionuclide was utilized.
• Use of an investigational agent within 4 weeks of Day 1 visit.
• Major surgery within 4 weeks prior to Day 1 visit.
• History of seizure or any condition that may predispose to seizures (e.g., prior cortical stroke or significant brain trauma) at any time in the past. History of loss of consciousness or transient ischemic attack within 12 months of screening.
• History of clinically significant cardiovascular disease including:
• Myocardial infarction or uncontrolled angina within 3 months;
• History of congestive heart failure New York Heart Association (NYHA) class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan performed within three months results in a left ventricular ejection fraction that is ≥ 45%;
• History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes);
• History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place.
• Clinically significant cardiovascular disease at screening including:
• Hypotension as indicated by systolic blood pressure \< 86 millimeters of mercury (mm Hg) at screening;
• Bradycardia as indicated by a heart rate of \< 45 beats per minute on the screening electrocardiogram (ECG) and on physical examination;
• Uncontrolled hypertension as indicated by at least 2 consecutive measurements of a resting systolic blood pressure \> 170 mmHg or diastolic blood pressure \> 105 mmHg at the screening visit.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Medivation, Inc.: collaborator

Study Sites (5)

Site US10003

Evanston, Illinois, 60201, United States

Location

Site US10006

Worcester, Massachusetts, 01605, United States

Location

Site US10004

New York, New York, 10029, United States

Location

Site US10001

Charleston, South Carolina, 29425, United States

Location

Site US10002

Myrtle Beach, South Carolina, 29572, United States

Location

Related Links

• Link to results on Astellas Clinical Study Results website

MeSH Terms

Conditions

Neoplasm Metastasis; Prostatic Neoplasms

Interventions

enzalutamide

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; 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: Clinical Trial Disclosure
• Organization: Astellas Pharma Inc.

astellas.resultsdisclosure@astellas.com

800-888-7704

Study Officials

• Medical Director, Oncology

  APGD, Medical Affairs, Americas

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2015
• First Posted: May 12, 2015
• Study Start: October 28, 2015
• Primary Completion: March 15, 2017
• Study Completion: March 15, 2017
• Last Updated: April 19, 2018
• Results First Posted: April 19, 2018

Record last verified: 2018-04

Locations

US (5)