TAK-700 in Castration Resistant Prostate Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Orteronel, 300 mg twice daily
|
Drug: Orteronel
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
Other Names:
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| Active Comparator: Bicalutamide 50 mg per day
|
Drug: Bicalutamide
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.
|
Outcome Measures
Primary Outcome Measures
- 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
- 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 []
Eligibility Criteria
Criteria
Inclusion criteria:
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Histologically confirmed diagnosis of prostate adenocarcinoma
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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)
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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)
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WHO (World health organization) performance status ≤ 2
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Life expectancy > 12 weeks
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Adequate bone marrow function (Absolute neutrophil count (ANC) 1500/μL; platelets 100,000/μL)
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Castrate serum levels of testosterone (< 50 ng/dL)
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Adequate renal function: calculated creatinine clearance > 40 mL/minute
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Adequate hepatic function:
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Bilirubin: total bilirubin 1.5 Upper limit of Normal (ULN)
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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
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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
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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
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Cardiac function:
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Screening calculated ejection fraction (Multi Gated Acquisition Scan (MUGA) scan, or by echocardiogram) must be ≥ 50%
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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
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Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed
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Absence of New York Heart Association Class III or IV heart failure
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Absence of Electrocardiogram (ECG) abnormalities of: Q-wave infarction, unless identified 6 or more months prior to screening and QTc interval > 470 msec
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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
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Prior radiotherapy but only for lymph nodes is allowed
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Prior or concomitant therapy:
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No intake of narcotic analgesia for bone pain
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No prior treatment with non-steroidal antiandrogens, within 6 months prior to randomization
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No anticancer therapy or treatment with another investigational agent within the last 4 weeks prior to randomization
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No prior therapy with TAK-700, ketoconazole, abiraterone, aminoglutethimide or MDV3100
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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)
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No known hypersensitivity to compounds related to TAK-700 or to TAK-700 excipients (refer to Investigator's brochure)
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No known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of TAK-700, including difficulty swallowing tablets
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No prior history of adrenal insufficiency
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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
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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
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No drug or alcohol abuse
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Onze Lieve Vrouw Ziekenhuis | Aals | Belgium | ||
| 2 | Cliniques Universitaires Saint-Luc | Brussels | Belgium | ||
| 3 | AZ Groeninge Kortrijk - Campus Vercruysselaan | Kortrijck | Belgium | ||
| 4 | CHU Dinant Godinne - UCL Namur | Yvoir | Belgium |
Sponsors and Collaborators
- European Organisation for Research and Treatment of Cancer - EORTC
Investigators
- Principal Investigator: Cora Sternberg, San Camillo Forlanini Hospitals, Rome, Italy
- Study Chair: Bertrand Tombal, Cliniques Universitaires de St Luc, Brussels, Belgium
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EORTC-1211-GUCG-IG
- 2012-002122-67