Trial record 1 of 1 for:    NCT01866423
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Orteronel in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01866423
Recruitment Status : Terminated (Not progressing toward scientific goals)
First Posted : May 31, 2013
Results First Posted : August 31, 2017
Last Update Posted : August 31, 2017
National Cancer Institute (NCI)
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
University of Southern California

Brief 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.

Condition or disease Intervention/treatment Phase
Adenocarcinoma of the Prostate Hormone-resistant Prostate Cancer Recurrent Prostate Cancer Stage IV Prostate Cancer Drug: orteronel Other: laboratory biomarker analysis Phase 2

Detailed Description:


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 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Trial of TAK-700 (Also Known as Orteronel) Without Prednisone for Metastatic Castration-Resistant Prostate Cancer
Actual Study Start Date : October 25, 2013
Actual Primary Completion Date : July 23, 2015
Actual Study Completion Date : July 26, 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Treatment (orteronel)
Patients receive orteronel 300 mg PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: orteronel
Given PO
Other Name: TAK-700
Other: laboratory biomarker analysis
Correlative studies

Primary Outcome Measures :
  1. Androgen Receptor (AR) Protein Expression Levels in CTCs [ Time Frame: Up to 4 weeks ]
    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 prostate-specific antigen (PSA) response.

  2. PSA Response, Defined as Occurrence of PSA Decline to Greater Than or Equal to 50% From Baseline [ Time Frame: At 12 weeks ]
    Standard descriptive methods will be used to summarize PSA. Values will be tabulated as outlined in the Prostate Cancer Working Group 2 (PCWG2) criteria and presented as Kaplan-Meier survival curves, as appropriate.

Secondary Outcome Measures :
  1. Best PSA Response [ Time Frame: Up to 24 weeks ]
    Values will be tabulated as outlined in the PCWG2 criteria and presented as Kaplan-Meier survival curves, as appropriate.

  2. Absolute Change in PSA [ Time Frame: Baseline to 24 weeks ]
    Values will be tabulated as outlined in the PCWG2 criteria and presented as Kaplan-Meier survival curves, as appropriate.

  3. Overall Response Rate Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and PCWG2 Criteria [ Time Frame: Up to 3 years ]
    Response will be tabulated descriptively with 95% confidence intervals (CIs) and Kaplan-Meier survival curves, as appropriate.

  4. Duration of Response Using RECIST Version 1.1 and PCWG2 Criteria [ Time Frame: Up to 3 years ]
    Response will be tabulated descriptively with 95% CIs and Kaplan-Meier survival curves, as appropriate.

  5. Number of Participants With Grade 3 or Higher Toxicity [ Time Frame: 30 days ]
    Summary of grade 3 (per Common Terminology Criteria for Adverse Events (CTCAE v4.0) or higher toxicities which generally is described as a severe reaction or symptom.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01866423

United States, California
USC Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
Sponsors and Collaborators
University of Southern California
National Cancer Institute (NCI)
Millennium Pharmaceuticals, Inc.
Principal Investigator: Mitchell Gross University of Southern California

Responsible Party: University of Southern California Identifier: NCT01866423     History of Changes
Other Study ID Numbers: 4P-13-1
NCI-2013-01013 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA014089 ( U.S. NIH Grant/Contract )
First Posted: May 31, 2013    Key Record Dates
Results First Posted: August 31, 2017
Last Update Posted: August 31, 2017
Last Verified: June 2017

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type