Orteronel in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer
Condition: Adenocarcinoma of the Prostate; Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage IV Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: orteronel; laboratory biomarker analysis
Intervention description: Given PO; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well orteronel works in treating patients with metastatic
      hormone-resistant prostate cancer. Orteronel may stop the growth of tumor cells by blocking
      some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed adenocarcinoma of the prostate

          -  Voluntary written informed consent before performance of any study-related procedure
             not part of normal medical care, with the understanding that consent may be withdrawn
             by the subject at any time without prejudice to future medical care

          -  Patients, even if surgically sterilized (i.e., status post vasectomy), who agree to
             practice effective barrier contraception during the entire study treatment period and
             for 4 months after the last dose of study drug, or

          -  Agree to completely abstain from intercourse

          -  Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be =<
             2.5 x the upper limit of normal (ULN)

          -  Total bilirubin =< 1.5 x ULN

          -  Estimated creatinine clearance using the Cockcroft-Gault formula must be > 40
             mL/minute

          -  Absolute neutrophil count (ANC) >= 1500 cells/microliter

          -  Platelet count >= 100,000 cells/microliter

          -  Testosterone < 50 ng/dL

          -  Screening calculated ejection fraction of >= 50% by multiple gated acquisition (MUGA)
             scan or echocardiogram; metastatic progression on primary androgen-deprivation therapy
             (medical or surgical castration)

          -  Progression requiring a change in oncologic therapy defined by any of the following:

               -  Radiographic progression: appearance or increase in measurable lesions on
                  cross-sectional imaging or appearance of one or more new lesions on bone scan *
                  Rising PSA (>= 2 ng/ml) which has risen on two occasions >= 1 week apart

               -  Clinical progression evidenced by increased pain or other cancer-related symptoms

          -  Patients should have recovered from prior oncologic therapies to a Common Terminology
             Criteria (CTC) grade =< 1 except stable neuropathy or alopecia at National Cancer
             Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade =< 2; if
             rapid clinical progression is documented by imaging, changes in PSA, or symptoms, then
             study treatment can begin >= 2 weeks from prior therapy; otherwise, the following time
             periods between prior anti-cancer therapies and study treatment day 1 will apply:

               -  >= 3 weeks for prior cytotoxic therapies

               -  >= 4 weeks for flutamide or nilutamide

               -  >= 6 weeks for bicalutamide

               -  >= 6 weeks since bone targeted radiopharmaceutical (e.g. samarium-153,
                  radium-223)

          -  Gonadotropin-releasing hormone (GnRH) agonists (leuprolide acetate, goserelin, etc.)
             or antagonists (degarelix, etc.) should be continued in patients without
             surgically-induced castrate androgen levels

          -  For chemotherapy naïve castration-resistant prostate cancer who are moderately
             symptomatic or who have hepatic metastasis: subjects must not be a candidate for
             docetaxel-based chemotherapy.

        Exclusion Criteria:

          -  History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing
             arrhythmias of grade > 2 (NCI CTCAE, version 4), thromboembolic events (e.g., deep
             vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any
             other cardiac condition (e.g. pericardial effusion, restrictive cardiomyopathy) within
             6 months prior to first dose of study drug; chronic stable atrial fibrillation on
             stable anticoagulant therapy is allowed

          -  New York Heart Association class III or IV heart failure

          -  Electrocardiogram (ECG) abnormalities of:

               -  Q-wave infarction, unless identified 6 or more months prior to screening

               -  Corrected QT (QTc) interval > 460 msec

          -  Patient has received other investigational drugs within 28 days before enrollment

          -  Diagnosed or treated for another malignancy within 2 years of enrollment, with the
             exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
             the skin, an in situ malignancy

          -  Known hypersensitivity to compounds related to TAK-700 or to TAK-700 excipients

          -  Uncontrolled hypertension despite appropriate medical therapy (blood pressure [BP] of
             greater than 160 mmHg systolic and 90 mmHg diastolic at 2 separate measurements no
             more than 60 minutes apart during the screening visit); Note: patients may be
             rescreened after adjustment of antihypertensive medications

          -  Known active chronic hepatitis B or C, life-threatening illness unrelated to cancer,
             or any serious medical or psychiatric illness that could, in the investigator's
             opinion, potentially interfere with participation in this study

          -  Likely inability to comply with the protocol or cooperate fully with the investigator
             and site personnel

          -  Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI
             absorption or tolerance of TAK-700, including difficulty swallowing tablets

          -  Prior treatment with >= 3 lines of cytotoxic chemotherapy for metastatic prostate
             cancer

          -  Prior treatment with TAK-700