5538S-14

CTSU A031201: Phase III Trial of Enzalutamide versus Enzalutamide Abiraterone and Prednisone For Castration-Resistant Metastatic Prostate Cancer

Type of Study
Cancer (Oncology) - Prostate
Location
Swedish Cancer Institute
Short Description

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.

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 (abiraterone acetate) and prednisone


Status
Open, enrolling
Principal Investigator
Gary Goodman, MD
Eligibility Notes

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
  • Measurable Disease - 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
  • 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 the following:


  • Bone lesions

  • Leptomeningeal disease

  • Ascites

  • Cancer-related pleural/pericardial effusion

  • Inflammatory breast disease

  • Lymphangitis cutis/pulmonis

  • Abdominal masses that are not confirmed and followed by imaging techniques

  • Cystic lesions

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:
  • 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

Prior Treatment:

  • 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)

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:


    • 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
Start Date
4/17/2014
More Info Link
clinicaltrials.gov
Phone
(206) 215-3086
Email
cancerresearch@swedish.org