Orteronel in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

NCT01866423 | Terminated Phase 2 Results DMC

• 4 other identifiers: 4P-13-1NCI-2013-01013IISR-2012-M000668P30CA014089
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  At 12 weeks

Secondary Outcomes (5)

• Best PSA Response

  Up to 24 weeks

• Absolute Change in PSA

  Baseline to 24 weeks

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

  Up to 3 years

• Duration of Response Using RECIST Version 1.1 and PCWG2 Criteria

  Up to 3 years

• Number of Participants With Grade 3 or Higher Toxicity

  30 days

Study Arms (1)

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.

Drug: orteronel; Other: laboratory biomarker analysis

Interventions

orteronel DRUG

Given PO

Also known as: TAK-700

Treatment (orteronel)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (orteronel)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

orteronel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

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.

Results Point of Contact

• Title: Victoria Soto, Project Specialist
• Organization: USC Norris Comprehensive Cancer Center

Victoria.Soto@med.usc.edu

323-865-0454

Study Officials

• Mitchell Gross

  University of Southern California

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2013
• First Posted: May 31, 2013
• Study Start: October 25, 2013
• Primary Completion: July 23, 2015
• Study Completion: July 26, 2016
• Last Updated: August 31, 2017
• Results First Posted: August 31, 2017

Record last verified: 2017-06

Locations

US (1)