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TerminatedNCT01866423Updated Aug 31, 2017Results posted

Orteronel in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

A Phase 2 interventional study of orteronel and laboratory biomarker analysis in Adenocarcinoma of the Prostate, Hormone-resistant Prostate Cancer and Recurrent Prostate Cancer, sponsored by University of Southern California. Terminated at 1 site in United States. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-08-31.

Sponsored by University of Southern California · Phase 2, Interventional, and Treatment

Why this study was terminated
Not progressing toward scientific goals
Phase
Phase 2
Study type
Interventional
Enrollment
4
Allocation
Not applicable
Ages
18 Years and older
Sex
Male
01

Study 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.

Read the 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.

02

Conditions studied

  • Adenocarcinoma of the Prostate
  • Hormone-resistant Prostate Cancer
  • Recurrent Prostate Cancer
  • Stage IV Prostate Cancer

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03

In context

Prostatic Neoplasms

6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,400 are open to participants now.

This study's enrollment of 4 is below the median of 58 across 4,822 interventional studies indexed under Prostatic Neoplasms.

Browse Prostatic Neoplasms studies →

Lead sponsor

University of Southern California is the lead sponsor of 773 studies on the registry; 135 are open to participants now.

Of its 68 completed or terminated interventional studies of FDA-regulated products, 32 (47%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
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

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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
4 participants (actual)

Study arms

  • 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 · Other: laboratory biomarker analysis

Interventions

  • Drugorteronel

    Given PO

    Also known as: TAK-700

  • Otherlaboratory biomarker analysis

    Correlative studies

06

What researchers measure

Primary outcomes

  1. Androgen Receptor (AR) Protein Expression Levels in CTCs

    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.

    Time frame: Up to 4 weeks

  2. PSA Response, Defined as Occurrence of PSA Decline to Greater Than or Equal to 50% From Baseline

    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.

    Time frame: At 12 weeks

Secondary outcomes

  1. Best PSA Response

    Values will be tabulated as outlined in the PCWG2 criteria and presented as Kaplan-Meier survival curves, as appropriate.

    Time frame: Up to 24 weeks

  2. Absolute Change in PSA

    Values will be tabulated as outlined in the PCWG2 criteria and presented as Kaplan-Meier survival curves, as appropriate.

    Time frame: Baseline to 24 weeks

  3. Overall Response Rate Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and PCWG2 Criteria

    Response will be tabulated descriptively with 95% confidence intervals (CIs) and Kaplan-Meier survival curves, as appropriate.

    Time frame: Up to 3 years

  4. Duration of Response Using RECIST Version 1.1 and PCWG2 Criteria

    Response will be tabulated descriptively with 95% CIs and Kaplan-Meier survival curves, as appropriate.

    Time frame: Up to 3 years

  5. Number of Participants With Grade 3 or Higher Toxicity

    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.

    Time frame: 30 days

07

Results

Posted Aug 31, 2017
Limitations and caveats
The trial was terminated early due to the discontinuation of the development program for the study drug, TAK-700 (orteronel) for prostate cancer.

Participant flow

Participants were recruited at the University of Southern California (USC) medical clinics from December 2013 to February 2014. Due to results of two phase III clinical trials in metastatic, castration resistant prostate cancer (mCRPC), the sponsor determined that the drug has not demonstrated a clinical profile sufficient to move forward in mCRPC.

Participant flow — Overall Study
MilestoneTreatment (Orteronel)
Started4
Completed0
Not completed4
Withdrew: Lack of efficacy3
Withdrew: Sponsor decision1

Outcome measures

PrimaryAndrogen Receptor (AR) Protein Expression Levels in CTCs

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.

Time frame:
Up to 4 weeks

No measurements were reported for this outcome.

PrimaryPSA Response, Defined as Occurrence of PSA Decline to Greater Than or Equal to 50% From Baseline

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.

Time frame:
At 12 weeks

No measurements were reported for this outcome.

SecondaryBest PSA Response

Values will be tabulated as outlined in the PCWG2 criteria and presented as Kaplan-Meier survival curves, as appropriate.

Time frame:
Up to 24 weeks

No measurements were reported for this outcome.

SecondaryAbsolute Change in PSA

Values will be tabulated as outlined in the PCWG2 criteria and presented as Kaplan-Meier survival curves, as appropriate.

Time frame:
Baseline to 24 weeks

No measurements were reported for this outcome.

SecondaryOverall Response Rate Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and PCWG2 Criteria

Response will be tabulated descriptively with 95% confidence intervals (CIs) and Kaplan-Meier survival curves, as appropriate.

Time frame:
Up to 3 years

No measurements were reported for this outcome.

SecondaryDuration of Response Using RECIST Version 1.1 and PCWG2 Criteria

Response will be tabulated descriptively with 95% CIs and Kaplan-Meier survival curves, as appropriate.

Time frame:
Up to 3 years

No measurements were reported for this outcome.

SecondaryNumber of Participants With Grade 3 or Higher Toxicity

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.

Time frame:
30 days
Reported as:
Count of participants · Participants
Number of Participants With Grade 3 or Higher Toxicity
ParticipantsTreatment (Orteronel)
Number of Participants With Grade 3 or Higher Toxicity1

Adverse events

Collected over Days 1, 8, 15, 21 of each cycle and treatment end (30 days after last dose or start of new treatment).. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment (Orteronel)0/4 (0%)1/4 (25%)3/4 (75%)
Most frequent serious events
Most frequent serious events
EventTreatment (Orteronel)
Abdominal PainGastrointestinal disorders1/4
AnemiaBlood and lymphatic system disorders1/4
HypertensionVascular disorders1/4
Platelet count decreasedInvestigations1/4
Most frequent other events
Showing 10 of 43
Most frequent other events
EventTreatment (Orteronel)
AnorexiaMetabolism and nutrition disorders3/4
CoughRespiratory, thoracic and mediastinal disorders3/4
FatigueGeneral disorders3/4
NauseaGastrointestinal disorders3/4
Abodminal PainGastrointestinal disorders2/4
Aspartate Aminotransferase increasedInvestigations2/4
Back painMusculoskeletal and connective tissue disorders2/4
ConstipationGastrointestinal disorders2/4
FeverGeneral disorders2/4
HyperglycemiaMetabolism and nutrition disorders2/4

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Treatment (Orteronel)
<=18 years0
Between 18 and 65 years1
>=65 years3
Sex: Female, Male
Sex: Female, Male(Participants)Treatment (Orteronel)
Female0
Male4
Region of Enrollment
Region of Enrollment(Participants)Treatment (Orteronel)
United States4
08

Study locations

1 site
  • USC Norris Comprehensive Cancer Center
    Los Angeles, California 90033, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 31, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01866423
Lead sponsor
University of Southern California
Collaborators
National Cancer Institute (NCI), Millennium Pharmaceuticals, Inc.
Responsible party
Sponsor
First posted
May 31, 2013
Start date
Oct 25, 2013
Primary completion
Jul 23, 2015
Completion
Jul 26, 2016
Results posted
Aug 31, 2017
Last update
Aug 31, 2017

Study contacts

Mitchell Gross
principal investigator · University of Southern California

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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This study is terminated, as verified in Jun 2017. You cannot join it, but the record below documents what was studied.

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