Phase III Trial of Enzalutamide (NSC# 766085) Versus Enzalutamide, Abiraterone and Prednisone for Castration Resistant Metastatic Prostate Cancer
Phase III Trial of Enzalutamide (NSC# 766085) Versus Enzalutamide, Abiraterone and Prednisone for Castration Resistant Metastatic Prostate Cancer
This randomized phase III trial studies enzalutamide to see how well it works compared to enzalutamide, abiraterone, and prednisone in treating patients with castration-resistant metastatic prostate cancer. Androgens can cause the growth of prostate cancer cells. Drugs, such as enzalutamide, abiraterone acetate, and prednisone, may lessen the amount of androgens made by the body.
Patients are randomized to one of two treatment groups: enzalutamide or enzalutamide, abiraterone and prednisone. Treatment will continue until disease progression or unacceptable toxicity. Patients are followed for clinical outcomes for a maximum of 5 years post study treatment. The primary and secondary objectives are described below.
Primary Objective:
To compare the overall survival of patients with progressive metastatic castration-resistant prostate cancer (CRPC) treated with either enzalutamide only or enzalutamide with abiraterone and prednisone
Secondary Objectives:
Eligibility Criteria:
Documentation of Disease - Progressive castration-resistant metastatic prostate cancer with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
Patients must have measurable or non-measurable disease:
Progressive Disease - Patients must have progressive disease at study entry defined as one or more of the following three criteria that occurred while the patient was on androgen deprivation therapy. For patients enrolling on the basis of soft tissue or bone progression, the baseline scan must show progression relative to a comparison scan. If the comparison scan is not available, the baseline scan report must reference the previous scan to document progression.
PSA progression defined by a minimum of two rising PSA levels with an interval of ≥ 1 week between each determination. Patients who received an anti-androgen must have progression documented by a minimum of two rising PSA levels with an interval of ≥ 1 week between each determination such that at least the second of these rises is ≥ 4 weeks since last flutamide, bicalutamide or nilutamide.
The PSA value at the screening should be ≥ 2 µg/L (2 ng/mL) .
Soft tissue disease progression defined by the protocol
Bone disease progression defined by the Prostate Cancer Working Group 2 (PCWG2) with two or more new lesions on bone scan
Prior Treatment
No treatment with prior taxane-based chemotherapy for metastatic disease
No prior enzalutamide, abiraterone or other novel antiandrogen or androgen synthesis inhibitor
No treatment with any of the following for prostate cancer within 4 weeks prior to enrollment:
No use of herbal products that may decrease PSA levels within 4 weeks prior to enrollment
No use of systemic steroids greater than the equivalent of 10 mg of prednisone/prednisolone per day within 4 weeks prior to enrollment
No prior use of ketoconazole for greater than 7 days
No prior radiation therapy or radionuclide therapy for the treatment of metastasis within four weeks prior to enrollment
Patients receiving bisphosphonate therapy or denosumab must have been on a stable dose for at least 4 weeks prior to enrollment
Patients must maintain ongoing androgen deprivation therapy with a GnRH analogue, antagonist, or bilateral orchiectomy (i.e., surgical or medical castration)
Patient History
No known or suspected brain metastases (NOTE: patients with treated epidural disease are allowed)
No planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery
No structurally unstable bone lesions suggesting impending fracture
No history of seizure or any condition that may increase the patient's seizure risk (e.g., prior cortical stroke, significant brain trauma). No history of transient ischemic attack (TIA) within 12 months of enrollment
No clinically significant cardiovascular disease including:
No gastrointestinal (GI) disorder that negatively affects absorption
No major surgery within 4 weeks prior to enrollment
Age and performance status
Required Initial Laboratory Values
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