|Phase III||Biomarker/Laboratory analysis, Treatment||Approved-not yet active||18 and over||NCI, Other||A031201|
This randomized phase III trial studies enzalutamide to see how well it works compared to enzalutamide, abiraterone acetate, 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.
Further Study Information
Patients are randomized to one of two treatment groups: enzalutamide or enzalutamide, abiraterone and prednisone. Treatment will continue until disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for clinical outcomes and death of a maximum of 5 years post registration. The primary and secondary objectives are described below.
1. To compare the overall survival of patients with progressive metastatic castration-resistant prostate cancer (CRPC) treated with either a) enzalutamide only or b) enzalutamide with abiraterone (abiraterone acetate) and prednisone.
1. To assess the grade 3 or higher toxicity profile and compare safety by treatment arm.
2. To assess and compare post-treatment prostate-specific antigen (PSA) declines by treatment arm.
3. To compare radiographic progression free survival defined by Prostate Cancer Working Group 2 (PCWG2), and objective response rate, by treatment arm.
4. To test for radiographic progression free survival (rPFS) treatment interaction in predicting overall survival.
5. To assess pre- and post-treatment measures of tumor burden and bone activity using sodium fluoride (NaF) positron emission tomography (PET)/computed tomography (CT) and technetium (Tc) methylene diphosphonate (MDP) bone scintigraphy and correlate these measures with overall survival.
6. To develop and validate prognostic and predictive models of overall survival that include baseline clinical and molecular markers.
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
• Lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 2 cm with conventional techniques or as ≥ 1 cm with spiral computed tomography (CT) scan
• 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 the following:
- Bone lesions
- Leptomeningeal disease
- Cancer-related pleural/pericardial effusion
- Inflammatory breast disease
- Lymphangitis cutis/pulmonis
- Abdominal masses that are not confirmed and followed by imaging techniques
- Cystic lesions
- 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:
- 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 after withdrawal (≥ 4 weeks since last flutamide or ≥ 6 weeks since last bicalutamide or nilutamide). The PSA value at the screening should be ≥ 2 µg/L (2 ng/mL)
- Soft tissue disease progression defined by Response Evaluation Criteria in Solid tumors (RECIST) 1.1
- Bone disease progression defined by the Prostate Cancer Working Group 2 (PCWG2) with two or more new lesions on bone scan
- No treatment with prior taxane-based chemotherapy for metastatic disease
- 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 one cycle of prior therapy is allowable
- No treatment with hormonal therapy (e.g., androgen receptor [AR] antagonists, 5 alpha reductase inhibitors, estrogens) other than gonadotropin-releasing hormone (GnRH) analogues or antagonists, chemotherapy, biologic therapy, investigational therapy, or immunotherapy for prostate cancer within 4 weeks of enrollment
- No prior enzalutamide, abiraterone, or other novel antiandrogen or androgen synthesis inhibitor
- 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 beta-emitting 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)
- 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:
- Myocardial infarction (MI) within 6 months
- Uncontrolled angina within 3 months
- Congestive heart failure (CHF) with New York Heart Association (NYHA) class 3 or 4, or patients with NYHA class 3 or 4 in the past, unless a screening echocardiogram (echo) or multi gated acquisition scan (MUGA) performed within three months demonstrates an ejection fraction (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 blood pressure [BP] < 86 mmHg) or bradycardia (< 50 bpm) at screening
- Uncontrolled hypertension (systolic BP > 170 mmHg or diastolic BP > 105 mmHg at screening)
- No gastrointestinal (GI) disorder that negatively affects absorption
- No major surgery within 4 weeks prior to enrollment
Age and performance status:
- Age ≥ 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Asymptomatic or mildly symptomatic from prostate cancer
Required Initial Laboratory Values:
- 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
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2 x ULN
- Albumin ≥ 3 g/dl
Trial Lead Organizations/Sponsors
Alliance for Clinical Trials in OncologyNational Cancer Institute
|Michael Morris||Study Chair|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01949337
ClinicalTrials.gov processed this data on January 15, 2014
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