Genetic and Molecular Mechanisms in Assessing Response in Patients With Prostate Cancer Receiving Enzalutamide Therapy
Condition: Castration-Resistant Prostate Carcinoma; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage III Prostate Adenocarcinoma AJCC v7; Stage IV Prostate Adenocarcinoma AJCC v7
MeSH terms: Carcinoma; Neoplasms; Adenocarcinoma; Prostatic Neoplasms; Neoplasms, Second Primary
Intervention: Enzalutamide
Intervention description: Given PO
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies genetic and molecular mechanisms in assessing response in
      patients with prostate cancer receiving enzalutamide therapy. Androgens can cause the growth
      of prostate cancer cells. Antihormone therapy, such as enzalutamide, may lessen the amount of
      androgens made by the body. Studying samples of tissue and blood in the laboratory from
      patients with prostate cancer may help doctors better understand castration-resistant
      prostate cancer. It may also help doctors make improvements in prostate cancer treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed adenocarcinoma of the prostate without pure
             small cell carcinoma; patients without histologically confirmed adenocarcinoma may be
             eligible if both the treating physician and the study principal investigator (PI)
             agree that the patient's history is unambiguously indicative of advanced
             adenocarcinoma

          -  Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH)
             analogue or orchiectomy (i.e., surgical or medical castration); patients who have not
             had an orchiectomy must maintain effective GnRH-analogue therapy for the duration of
             the trial

          -  Radiographic evidence of regional or distant metastases with suspected tumor in an
             area that is safe to biopsy

          -  Willingness to undergo a tumor biopsy at baseline and at disease progression

          -  Serum testosterone level < 50 ng/dL at screening

          -  Progressive disease by PSA or imaging in the setting of medical or surgical
             castration; disease progression for study entry is defined as one or more of the
             following three criteria:

               -  PSA evidence for progressive prostate cancer which consists of a PSA level of at
                  least 2 ng/ml which has risen on at least 2 successive occasions, at least 1 week
                  apart; if the confirmatory PSA value is less than the screening value, then an
                  additional PSA value greater than #2 will be required to document progression of
                  >= 1 week

                    -  PSA values to be obtained >= 1 week apart

               -  Soft tissue disease progression defined by Response Evaluation Criteria in Solid
                  Tumors (RECIST) 1.1

               -  Bone disease progression defined by two or more new lesions on bone scan

          -  Patient's physician has already recommended enzalutamide for treatment of progression

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

          -  Willing and able to give informed consent

          -  Estimated life expectancy >= 6 months

          -  Subjects who have partners of childbearing potential must be willing to use a method
             of birth control with adequate barrier protection as determined to be acceptable by
             the principal investigator and sponsor during the study and for 1 week after last
             study drug administration

          -  A minimum of 4 weeks elapsed off of anti-androgen therapy prior to enrollment for
             flutamide and 6 weeks for bicalutamide and nilutamide without evidence of an
             anti-androgen withdrawal response; patients who NEVER HAD A PSA decline with the most
             recent anti-androgen therapy or in whom the response to the most recent anti-androgen
             was for < 3 months require only a 2 week washout period prior to first dose of study
             drug

          -  A minimum of 4 weeks from prior systemic anti-cancer therapies or 3 weeks for
             radiation treatment prior to enrollment is required

        Exclusion Criteria:

          -  Severe, concurrent disease, infection, or co-morbidity that, in the judgment of the
             investigator, would make the patient inappropriate for enrollment

          -  Previous treatment with docetaxel for metastatic prostate cancer

          -  Known metastases in the brain or active epidural disease (NOTE: patients with treated
             epidural disease are allowed)

          -  Absolute neutrophil count < 1,000/uL

          -  Platelet count < 75,000/uL

          -  Hemoglobin < 9 g/dL at the screening visit; (NOTE: subject may not have received any
             growth factors or blood transfusions within seven days of the hematologic laboratory
             values obtained at the screening visit)

          -  Total bilirubin (TBL) > 2.5 times the upper limit of normal at the screening visit

          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times the
             upper limit of normal at the screening visit

          -  Creatinine (Cr) > 2 mg/dL at the screening visit

          -  Prothrombin time (PT) or international normalized ratio (INR) and a partial
             thromboplastin time (PTT) > 1.5 times the upper limit of normal

          -  Previous treatment with an agent that blocks adrenal androgen synthesis (e.g.
             abiraterone acetate, TAK-700, TOK-001, ketoconazole) or second generation androgen
             receptor (AR) antagonists (e.g., BMS 641988, ARN-509,TOK-001)

          -  Systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day
             within 4 weeks of study drug administration are prohibited

          -  Structurally unstable bone lesions suggesting impending fracture

          -  Previous treatment with enzalutamide (MDV3100)

          -  Medical contraindications to stopping aspirin, Coumadin or other anticoagulants prior
             to image-guided tumor biopsies; follow institutional guidelines when determining drugs
             to avoid and length of washout

          -  Plans to initiate treatment with an investigational agent during the study

          -  History of seizure or condition that may predispose to seizure; also, history of loss
             of consciousness or transient ischemic attack within 12 months of (day 1 visit)

          -  Concomitant use of the strong CYP2C8 inhibitors gemfibrozil or trimethoprim (Bactrim)

          -  History of known malabsorption syndrome or prior surgery(ies) that may lead to
             malabsorption

          -  Use of herbal products that may have hormonal anti-prostate cancer activity and/or are
             known to decrease PSA levels (e.g., saw palmetto) within 4 weeks of study drug
             administration (day 1)

          -  Use of the following drugs within 4 weeks of study drug administration: 5
             alpha-reductase inhibitors (finasteride, dutasteride), estrogens, Cyproterone acetate,
             biologic, or other agents with anti-tumor activity against prostate cancer, and
             androgens (testosterone, dihydroepiandrosterone [DHEA], etc.)

          -  A second active malignancy except adequately treated non-melanoma skin cancer or other
             non-invasive or in situ neoplasm