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Phase 2 Trial of TAK-700 (Orteronel) Without Prednisone for Metastatic Castration-Resistant Prostate Cancer

Phase 2
18 Years
Not Enrolling
Adenocarcinoma of the Prostate, Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer, Stage IV Prostate Cancer

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Trial Information

Phase 2 Trial of TAK-700 (Orteronel) Without Prednisone for Metastatic Castration-Resistant Prostate Cancer


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).


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

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not part of normal medical care, with the understanding that consent may be withdrawn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

- Absolute neutrophil count (ANC) >= 1500/uL

- Platelet count >= 100,000/uL

- 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

- 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,

- Gonadotropin-releasing hormone (GnRH) agonists (leuprolide acetate, goserelin, etc.)
or antagonists (degarelix, etc.) should be continued in patients without
surgically-induced castrate androgen levels

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

- Prior treatment with TAK-700

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

AR protein expression levels in CTCs

Outcome Description:

The two-sample t-test will be used. Once association between AR protein expression levels and response is established, graphical methods such as receiver-operator curves (ROC) or more quantitative methods such as the maximal chi-square method to determine whether there might be a cut-point with either great sensitivity or great specificity (or both) for identifying a cohort with either a high or low likelihood of PSA response.

Outcome Time Frame:

Up to 4 weeks

Safety Issue:


Principal Investigator

Mitchell Gross

Investigator Role:

Principal Investigator

Investigator Affiliation:

USC/Norris Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

June 2013

Completion Date:

June 2016

Related Keywords:

  • Adenocarcinoma of the Prostate
  • Hormone-resistant Prostate Cancer
  • Recurrent Prostate Cancer
  • Stage IV Prostate Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Prostatic Neoplasms



USC Norris Comprehensive Cancer CenterLos Angeles, California  90089