A Multicenter, Open-label, Single-arm, Study of Enzalutamide Re-Treatment in Metastatic Castration-Resistant Prostate Cancer, As First Treatment Post-Chemotherapy in Patients Who Have Previously Received Enzalutamide in the Pre-Chemotherapy Setting
Overview
- Phase
- Phase 4
- Intervention
- Enzalutamide
- Conditions
- Metastatic Castration Resistant Prostate Cancer
- Sponsor
- Astellas Pharma Global Development, Inc.
- Enrollment
- 4
- Locations
- 5
- Primary Endpoint
- Radiographic Progression Free Survival (rPFS)
- Status
- Terminated
- Last Updated
- 8 years ago
Overview
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.
Detailed Description
Participants received treatment with open-label enzalutamide, until radiographic or clinical progression (such as pathological fracture, cord compression, worsened pain requiring radiation therapy, or opioid analgesic dose increase or initiation), or unacceptable toxicity. Participants were to be allowed to continue enzalutamide until the next treatment was initiated. If another non-cytotoxic, non-investigational, antineoplastic agent was initiated after protocol-defined progression had been determined, enzalutamide was to be continued as long as the participant was tolerating enzalutamide and continued androgen deprivation therapy. Participants were to have a safety follow-up visit approximately 30 days following the last dose of study drug or prior to the initiation of a subsequent anti-cancer drug or investigational agent, whichever occurred first. Disease progression and survival were to be followed every 12 weeks for a maximum of 3 years from first dose. The study should have ended when the last participant has been followed for 1 year from the date of first dose, but the study was terminated and results up to the last date of evaluation (15 March 2017) are reflected in this disclosure.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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);
Arms & Interventions
Enzalutamide
Participants received 160 mg enzalutamide orally once daily until radiographic or clinical progression, or unacceptable toxicity.
Intervention: Enzalutamide
Outcomes
Primary Outcomes
Radiographic Progression Free Survival (rPFS)
Time Frame: From first dose of study drug up to date of last evaluation of 15 March 2017 (approximately 17 months)
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).
Secondary Outcomes
- 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))
- Overall Survival(From first dose of study drug 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))
- Number of Participants With Adverse Events(From first dose of study drug up to date of last evaluation of 15 March 2017 (approximately 17 months))