TAK-700 in Castration Resistant Prostate Cancer

European Organisation for Research and Treatment of Cancer (EORTC)

Status and phase: Withdrawn; Phase 2

Conditions: Prostate Cancer

Treatments: Drug: Bicalutamide; Drug: Orteronel

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT01658527

2012-002122-67 (EudraCT Number)

EORTC-1211-GUCG-IG

Details and patient eligibility

About

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.

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 2 patient groups

Orteronel, 300 mg twice daily

Experimental group

Treatment:

Drug: Orteronel

Bicalutamide 50 mg per day

Active Comparator group

Treatment:

Drug: Bicalutamide