Prostate Cancer
Conditions
Keywords
metastatic, prostate cancer
Brief 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.
Interventions
DRUGOrteronel
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
DRUGBicalutamide
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.
Sponsors
European Organisation for Research and Treatment of Cancer - EORTC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| Time to PSA (Prostate specific antigen) progression and PSA change from baseline | — |
| Overall survival | — |
| RECIST (Response Evaluation Criteria In Solid Tumors) response in patients presenting with measurable disease | — |
| 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 | — |
| Safety according to Common Terminology Criteria for Adverse Events, version 4.03 | — |
Countries
Belgium
Outcome results
None listed