tak-700 in castration resistant prostate cancer

Conditions: Prostate Cancer

Summary: 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.


Eligibility criteria:
inclusion criteria: * 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/μl; platelets 100,000/μl) * 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 exclusion criteria * 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

Keywords: metastatic prostate cancer