Clinical trial NCT01658527: TAK-700 in Castration Resistant Prostate Cancer
Official title: 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.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: metastatic
prostate cancer
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2012-08-07
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: The primary endpoint of the trial is clinical progression free survival.
Secondary outcomes:
measure: RECIST (Response Evaluation Criteria In Solid Tumors) response in patients presenting with measurable disease
measure: Time to PSA (Prostate specific antigen) progression and PSA change from baseline
measure: Overall survival
measure: Safety according to Common Terminology Criteria for Adverse Events, version 4.03
measure: Pain (when an SAE (Serious Adverse Event)) or pain requiring initiation of narcotic analgesia
measure: Skeletal related events, including requirement to initiate chemotherapy, radiotherapy, cord compression or requirement for surgery to the bone
Other outcomes:
Locations:
city: Aals
country: Belgium
facility: Onze Lieve Vrouw Ziekenhuis
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Kortrijck
country: Belgium
facility: AZ Groeninge Kortrijk - Campus Vercruysselaan
city: Yvoir
country: Belgium
facility: CHU Dinant Godinne - UCL Namur
Study officials:
affiliation: San Camillo Forlanini Hospitals, Rome, Italy
name: Cora Sternberg
role: PRINCIPAL_INVESTIGATOR
affiliation: Cliniques Universitaires de St Luc, Brussels, Belgium
name: Bertrand Tombal
role: STUDY_CHAIR
References: