TAK-700 in Castration Resistant Prostate Cancer

Prostate Cancer Clinical Trial

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.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01658527
• Other study ID #: EORTC-1211-GUCG-IG
• Secondary ID: 2012-002122-67
• Status: Withdrawn
• Phase: Phase 2
• First received: July 27, 2012
• Last updated: June 9, 2016
• Start date: January 2014
• Est. completion date: January 2017

Study information

• Verified date: June 2016
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2017
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

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
• 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.

Locations

Country	Name	City	State
Belgium	Onze Lieve Vrouw Ziekenhuis	Aals
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	AZ Groeninge Kortrijk - Campus Vercruysselaan	Kortrijck
Belgium	CHU Dinant Godinne - UCL Namur	Yvoir

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		No
Secondary	RECIST (Response Evaluation Criteria In Solid Tumors) response in patients presenting with measurable disease			No
Secondary	Time to PSA (Prostate specific antigen) progression and PSA change from baseline			No
Secondary	Overall survival			No
Secondary	Safety according to Common Terminology Criteria for Adverse Events, version 4.03			Yes
Secondary	Pain (when an SAE (Serious Adverse Event)) or pain requiring initiation of narcotic analgesia			No
Secondary	Skeletal related events, including requirement to initiate chemotherapy, radiotherapy, cord compression or requirement for surgery to the bone			No