Orteronel in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

NCT ID: NCT01866423

Last Updated: 2017-08-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-25
• Study Completion Date: 2016-07-26

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.

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

orteronel

Intervention Type: DRUG

Given PO

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

orteronel

Given PO

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

TAK-700

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

University of Southern California

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mitchell Gross

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Locations

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

Countries

United States

Other Identifiers

NCI-2013-01013

Identifier Type: REGISTRY

Identifier Source: secondary_id

IISR-2012-M000668

Identifier Type: -

Identifier Source: secondary_id

P30CA014089

Identifier Type: NIH

Identifier Source: secondary_id

View Link

4P-13-1

Identifier Type: -

Identifier Source: org_study_id