Phase II randomized comparative trial of TAK-700 (Orteronel) versus bicalutamide in metastatic prostate cancer patients failing 1st line treatment with LHRH agonists or surgical castration.
- Conditions
- Metastatic prostate cancer patients failing 1st line treatment with LHRH agonists or surgical castrationMedDRA version: 16.1Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-002122-67-ES
- Lead Sponsor
- European Organisation for Research and Treatment of Cancer (EORTC)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 200
?Histologically confirmed diagnosis of prostate adenocarcinoma
?Metastatic disease in bone or other lesions documented by imaging. Abnormal 99mTc-bone scan imaging must be confirmed by Computed Tomography (CT) Scan or Magnetic resonance Imaging (MRI)
?Progressive disease following 1st line androgen deprivation therapy with LHRH (luteinizing hormone-releasing hormone) Agonists or surgical castration. Recommendations of Prostate Cancer Working Group 2 (PCWG2)
?WHO (World health organization) performance status ? 2
?Life expectancy > 12 weeks
?Adequate bone marrow function (Absolute neutrophil count (ANC) 1500/?L; platelets 100,000/?L)
?Castrate serum levels of testosterone (< 50 ng/dL)
?Adequate renal function: calculated creatinine clearance > 40 mL/minute
?Adequate hepatic function:
?Bilirubin: total bilirubin 1.5 Upper limit of Normal (ULN)
?Asparate aminotransferase (AST) and/or Alanine aminotransferase (ALT) ? 2.5 x ULN in the absence of liver metastases or ? 5 x ULN if liver metastases are present
?Patients of reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 4 months following the last study treatment. A highly effective method of birth control is defined as those that result in low failure rate (i.e. less than 1% per year) when used consistently and correctly
?Before patient registration/randomization, written informed consent must be given according to ICH/GCP (International conference on Harmonization-Good Clinical Practices), and national/local regulations
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100
?Cardiac function:
?Screening calculated ejection fraction (Multi Gated Acquisition Scan (MUGA) scan, or by echocardiogram) must be ? 50%
?No history of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias of Grade > 2 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
?Absence of New York Heart Association Class III or IV heart failure
?Absence of Electrocardiogram (ECG) abnormalities of: Q-wave infarction, unless identified 6 or more months prior to screening and QTc interval > 470 msec
?No uncontrolled hypertension despite appropriate medical therapy defined as blood pressure >160/90 mmHg at 2 separate measurements no more than 60 minutes apart during the Screening visit
?Prior radiotherapy but only for lymph nodes is allowed
?Prior or concomitant therapy:
?No intake of narcotic analgesia for bone pain
?No prior treatment with non-steroidal antiandrogens, within 6 months prior to randomization
?No anticancer therapy or treatment with another investigational agent within the last 4 weeks prior to randomization
?No prior therapy with TAK-700, ketoconazole, abiraterone, aminoglutethimide or MDV3100
?Patients taking bisphosphonates or denosumab are eligible if they have received a stable dose for 4 weeks or more prior to randomization. (These treatments may then be continued on study)
?No known hypersensitivity to compounds related to TAK-700 or to TAK-700 excipients (refer to Investigator's brochure)
?No known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of TAK-700, including difficulty swallowing tablets
?No prior history of adrenal insufficiency
?No prior history of malignancies other than prostate adenocarcinoma (except for basal cell or squamous cell carcinoma of the skin), or the patient has been free of malignancy for a period of 3 years prior to first dose of study drug
?No 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
?No drug or alcohol abuse
?Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary end point(s): The primary endpoint of the trial is clinical progression free survival.;Timepoint(s) of evaluation of this end point: The primary endpoint is counted from the day of randomization to the day of first diagnosis of clinical progression or the day of death of any cause that occurs prior or at the data analysis cut-off date.;Main Objective: The objective of this randomized phase II open label trial is to determine the anti-tumor activity of TAK-700 (Orteronel) as compared to bicalutamide in terms of clinical progression-free survival in prostate cancer patients who failed 1st line treatment with LHRH (luteinizing hormone-releasing hormone) agonists or surgical castration.;Secondary Objective: Not Applicable
- Secondary Outcome Measures
Name Time Method Secondary end point(s): -RECIST 1.1 response in patients presenting with measurable disease<br>-Time to PSA progression and PSA change from baseline<br>-Overall survival<br>-Safety according to Common Terminology Criteria for Adverse Events, version 4.03<br>-Pain (when an SAE) or pain requiring initiation of narcotic analgesia<br>-Skeletal related events, including pathologic bone fractures (vertebral or non-vertebral), spinal cord compression, surgery to bone, focal radiation therapy to bone, a change of antineoplastic therapy to treat bone pain and hypercalcemia.;Timepoint(s) of evaluation of this end point: Time to PSA progression will be counted from the day of randomization to the day of first diagnosis of PSA progression.