Orteronel in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

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.

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not part of normal medical care, with the understanding that consent may be withdrawn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