Title Phase III Trial fo Enzalutamide versus Enzalutamide, Abiraterone and Prednisone for castration resistant metastatic prostate cancer
Hospital Beachwood, Fairview, Florida Weston, Hillcrest, Independence, Main Campus, Mansfield, North Coast Cancer, South Pointe, Strongsville, Wooster
Phase Phase 3
- To compare the overall survival of patients with progressive metastatic CRPC treated with either a) enzalutamide only or b) enzalutamide with abiraterone and prednisone
- To assess the grade 3 or higher toxicity profile and compare safety by treatment arm
- To assess and compare post-treatment PSA declines by treatment arm
- To compare radiographic progression free survival defined by Prostate Cancer Working Group 2 (PCWG2), and objective response rate, by treatment arm
- To test for fPFS treatment interaction in predicting overall survival.
- To assess pre- and post- treatment measures of tumor burden and bone activity using NaF PET/CT and Tc MDP bone scintigraphy and correlate these measures with overall survival
- To develop and validate prognostic and predictive models of overall survival that include baseline clinical and molecular markers
- 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
- Measurable Disease
For visceral or extra-nodal lesions to considered measurable, they must be ≥ 10 mm in one dimension, using spiral CT.
For lymph nodes to be considered measurable (i.e., target or evaluable lesions), they must be ≥ 20 mm in at least one dimension, using spiral CT.
- Non-measurable Disease
All other lesions, including small lesions (longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan) and truly non-measurable lesions.
Lesions that are considered non-measurable include bone lesions (only).
- 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 ≥ week between each determination such that at least the second of these rises is ≥ 4 weeks since last flutamide or ≥ 6 weeks since last bicalutamide or nilutamide. The PSA value at the screening should be ≥ 2 μg/L (2ng/mL)
- Soft tissue disease progression defined by Section 13.2.3.
- Bone disease progression defined by PCWG2 with two or more new lesions on bone scan.
- Patients who received prior taxane-based chemotherapy as neoadjuvant or adjuvant therapy for local disease, or who received taxane-based therapy in the PSA clinical (non-metastatic) state is allowable provided that the total duration of exposure was six cycles or less and chemotherapy was completed more than 6 months prior to registration.
- Taxane-based chemotherapy that was aborted due to allergic reactions or intolerance to chemotherapy and therefore received 1 cycle of prior therapy is allowable.
- Hormonal therapy (e.g., AR antagonists, 5 alpha reductase inhibitors, estrogens).
Note: Treatment with bicalutamide and nilutamide within 6 weeks prior to enrollment is not allowed. Treatment with flutamide within 4 weeks prior to enrollment is not allowed. Treatment with all other GnRH analogues or antagonists is allowed.
- Biologic therapy
- Investigational therapy
- MI within 6 months
- Uncontrolled angina within 3 months
- CHF with NYHA class 3 or 4, or patients with NYHA class 3 or 4 in the past, unless a screening echo or MUGA performed within three months demonstrates and EF>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
- Hypotension (systolic BP < 86 mmHg) or bradycardia (< 50 bpm) at screening
- Uncontrolled hypertension (systolic BP > 170 mmHg or diastolic BP > 105 mmHg at screening
A score of 0-1 on BPI-SF Question #3 (worst pain in last 24 hours) will be considered asymptomatic, and a score of 2-3 will be considered mildly symptomatic (see Appendix II)
- Granulocytes ≥ 1,500/μL
- Platelet count ≥ 100,000/μL
- Hemoglobin ≥ 9 g/dL
- Creatinine ≤ 2 x upper limits of normal (ULN)
- Bilirubin ≤ 1.5 x ULN
- AST or ALT ≤ 2 x ULN
- Albumin ≥ 3 g/dL
- Serum Testosterone ≤ 50 ng/dL (1.7 nmol/L)