Patient case: 70-year-old male with prostate cancer; genetic feature: PTEN

Clinical trial: Orteronel in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

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.

Detailed description: PRIMARY OBJECTIVES:
  I. To assess the relationship between circulating tumor cell (CTC)-based androgen receptor (AR) expression level and >=-50% prostate-specific antigen (PSA) decline following 12 weeks of therapy with TAK-700 (orteronel).
  SECONDARY OBJECTIVES:
  I. To assess changes in PSA and CTC levels and time to PSA progression (best response, decline at 12 weeks as continuous variable, etc.) with or without prior docetaxel-based treatment.
  II. To assess measurable disease response and time to radiographic disease progression for castration-resistant prostate cancer (CRPC) with or without prior docetaxel-based treatment.
  III. To explore relationships between endocrine and clinical responses.
  IV. To confirm the safety of TAK-700 administered without prednisone in patients with metastatic CRPC.
  OUTLINE: Patients receive orteronel orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Eligibility: 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care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/uL
  -  Platelet count >= 100,000/uL
  -  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

Relevance to patient case: not relevant