Adenocarcinoma of the ProstatePhase 2NCT01866423

Orteronel in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

A Phase 2 study testing orteronel and laboratory biomarker analysis in people with Adenocarcinoma of the Prostate and Hormone-resistant Prostate Cancer, run by University of Southern California at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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 more about this study

Who is it for?: Ages 18 years and older, men only
Conditions the study is for: Adenocarcinoma of the Prostate, Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer
What is being tested?: orteronel and laboratory biomarker analysis
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 4 participants
Where: 1 siteUnited States
Study dates: 25 Oct 2013to 26 Jul 2016
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Men only
No healthy volunteers
Adult, Older adult

Who may be able to join

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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care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

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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.

Who cannot join

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

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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

Trial locations and contacts

1 site in 1 country.

United States1 site

USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033

Other trials in United States

About this study

Official title: Phase 2 Trial of TAK-700 (Also Known as Orteronel) Without Prednisone for Metastatic Castration-Resistant Prostate Cancer

Read the detailed description

PRIMARY OBJECTIVES:

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:

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.

Conditions: Adenocarcinoma of the Prostate, Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer, Stage IV Prostate Cancer
Being tested: orteronel, laboratory biomarker analysis
Medical subject headings: Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

orteronelDrug
Also called TAK-700
Given PO
laboratory biomarker analysisOther
Correlative studies

Study groups in NCT01866423
Study group	Role	What they receive
Treatment (orteronel)	Experimental	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. Receives: Drug: orteronel; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Up to 4 weeks
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.
Measured: At 12 weeks

Secondary outcomes (5)

Best PSA Response
Values will be tabulated as outlined in the PCWG2 criteria and presented as Kaplan-Meier survival curves, as appropriate.
Measured: Up to 24 weeks
Absolute Change in PSA
Values will be tabulated as outlined in the PCWG2 criteria and presented as Kaplan-Meier survival curves, as appropriate.
Measured: Baseline to 24 weeks
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.
Measured: Up to 3 years
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.
Measured: Up to 3 years
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.
Measured: 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Oct 201326 Jul 2016

First posted31 May 2013 (estimated)
Study start25 Oct 2013
Primary completion23 Jul 2015
Study completion26 Jul 2016

Why it stopped: Not progressing toward scientific goals

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Adenocarcinoma of the ProstateStudies of the same condition, open and under way.
More trials run by University of Southern CaliforniaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 4 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01866423
Sponsor's protocol ID: 4P-13-1
Other IDs: NCI-2013-01013, IISR-2012-M000668, P30CA014089
Status last verified: Jun 2017
First submitted: 28 May 2013
Last updated: 31 Aug 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
ARCTIC: Liquid Biomarkers in the Prospective Androgen Receptor Signaling Inhibitors (ARSI) Resistance Clinical Trials
Prostate Cancer, Prostate Adenocarcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
Active, not recruitingPhase 1
Hypofractionated Accelerated Pelvic Nodal Radiotherapy (GCC 2048)
Prostate Cancer, Prostate Adenocarcinoma
Not yet recruitingPhase 2
Testing the Anti-cancer Drug DSP-5336 (Enzomenib) in Prostate Cancer
Metastatic Castration-Resistant Prostate Adenocarcinoma, Stage IVB Prostate Cancer AJCC v8
RecruitingPhase 2
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
Bladder Adenocarcinoma, Bladder Clear Cell Adenocarcinoma

All Adenocarcinoma of the Prostate trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 2 Trial of TAK-700 (Also Known as Orteronel) Without Prednisone for Metastatic Castration-Resistant Prostate Cancer
ClinicalTrials.gov ID: NCT01866423
Acronym / sponsor ID: 4P-13-1
Conditions: Adenocarcinoma of the Prostate, Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer, Stage IV Prostate Cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Not progressing toward scientific goals
Enrolment: 4 participants (actual)
Lead sponsor: University of Southern CaliforniaUniversity, hospital or other
Collaborators: National Cancer Institute (NCI), Millennium Pharmaceuticals, Inc.
Study start: 25 Oct 2013 (actual)
Primary completion: 23 Jul 2015 (actual)
Study completion: 26 Jul 2016 (actual)
First posted: 31 May 2013 (estimated)
Results: Posted 31 Aug 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

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:

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 design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment (orteronel)	Experimental	Drug: orteronel, Other: laboratory biomarker analysisPatients receive orteronel 300 mg PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who may qualify

Ages: 18 years and older
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (21 listed)

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)

Key exclusion criteria (14 listed)

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:
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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
orteronelAlso: TAK-700Given PO	Drug	Treatment (orteronel)
laboratory biomarker analysisCorrelative studies	Other	Treatment (orteronel)

Primary outcome

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.
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.

5 secondary outcomes

Best PSA Response
Time frame: Up to 24 weeks
Absolute Change in PSA
Time frame: Baseline to 24 weeks
Overall Response Rate Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and PCWG2 Criteria
Time frame: Up to 3 years
Duration of Response Using RECIST Version 1.1 and PCWG2 Criteria
Time frame: Up to 3 years
Number of Participants With Grade 3 or Higher Toxicity
Time frame: 30 days

Results and safety

Results posted to the registry on 31 Aug 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment (Orteronel)	4	0

Primary outcome: Androgen Receptor (AR) Protein Expression Levels in CTCs

Time frame: Up to 4 weeks

Population analysed: Only 4 patients were accrued to this trial. No data analysis was performed.

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

Time frame: At 12 weeks

Population analysed: Only 4 patients were accrued to this trial. No data analysis was performed.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Days 1, 8, 15, 21 of each cycle and treatment end (30 days after last dose or start of new treatment).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment (Orteronel)	1 of 4 (25%)	3 of 4 (75%)	0 of 4

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

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Adenocarcinoma of the Prostate

RecruitingObservational study
ARCTIC: Liquid Biomarkers in the Prospective Androgen Receptor Signaling Inhibitors (ARSI) Resistance Clinical Trials
Prostate Cancer, Prostate Adenocarcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
Active, not recruitingPhase 1
Hypofractionated Accelerated Pelvic Nodal Radiotherapy (GCC 2048)
Prostate Cancer, Prostate Adenocarcinoma
Not yet recruitingPhase 2
Testing the Anti-cancer Drug DSP-5336 (Enzomenib) in Prostate Cancer
Metastatic Castration-Resistant Prostate Adenocarcinoma, Stage IVB Prostate Cancer AJCC v8
RecruitingPhase 2
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
Bladder Adenocarcinoma, Bladder Clear Cell Adenocarcinoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mitchell Gross principal investigator

University of Southern California

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 31 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Androgen Receptor (AR) Protein Expression Levels in CTCs (time frame: Up to 4 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01866423.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2017.