TAK-700 in Castration Resistant Prostate Cancer

Study Overview
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Brief Summary
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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.

Official Title
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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
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Prostate Cancer

Intervention / Treatment
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* Drug: Orteronel
* Drug: Bicalutamide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orteronel, 300 mg twice daily<br> | Drug: Orteronel<br>* Tak-700 will be administered until disease progression, diagnosis of a second malignancy, patient refusal to continue the treatment, excessive toxicity precluding further therapy according to protocol and /or according to the responsible physician. Upon progression, patient may stay on study medication until the initiation of a new therapy<br>* Other names: TAK 700;|
| Active Comparator: Bicalutamide 50 mg per day<br> | Drug: Bicalutamide<br>* Bicalutamide will be given at the standard daily dose of 50 mg PO (per os). Bicalutamide will be maintained until disease progression diagnosis of a second malignancy, patient refusal to continue the treatment, excessive toxicity precluding further therapy according to protocol and /or according to the responsible physician.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint of the trial is clinical progression free survival. | The primary endpoint of the trial is clinical progression free survival. In this protocol, it is defined according to the recommendations of the Prostate-Cancer clinical trials Working Group 2 and referred to as the PCWG2 for the setting delay/prevent progression. |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RECIST (Response Evaluation Criteria In Solid Tumors) response in patients presenting with measurable disease |  |  | 
| Time to PSA (Prostate specific antigen) progression and PSA change from baseline |  |  | 
| Overall survival |  |  | 
| Safety according to Common Terminology Criteria for Adverse Events, version 4.03 |  |  | 
| Pain (when an SAE (Serious Adverse Event)) or pain requiring initiation of narcotic analgesia |  |  | 
| Skeletal related events, including requirement to initiate chemotherapy, radiotherapy, cord compression or requirement for surgery to the bone |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic, prostate cancer