Orteronel Maintenance Therapy in Patients With Metastatic Castration Resistant Prostate Cancer and Non-progressive Disease After First-line Docetaxel Therapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Swiss Group for Clinical Cancer Research
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
First received: September 13, 2012
Last updated: April 22, 2014
Last verified: April 2014

The main objective of this multicenter, randomized, double-blind, placebo-controlled phase III trial is to assess the impact of maintenance orteronel on disease progression and hence on quality of life in patients with metastatic castration-resistant prostate cancer who have achieved at lease disease stabilization after first line chemotherapy with docetaxel.

Condition Intervention Phase
Prostate Cancer
Drug: Orteronel
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Orteronel Maintenance Therapy in Patients With Metastatic Castration Resistant Prostate Cancer and Non-progressive Disease After First-line Docetaxel Therapy: a Multicenter Randomized Double-blind Placebo-controlled Phase III Trial.

Resource links provided by NLM:

Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • Event free survival (EFS) [ Time Frame: At baseline; every 4 weeks until disease progression (estimated up to 1 year) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Adverse events (AEs) [ Time Frame: Throughout treatment phase (estimated up to 1 year) until 30 days after last drug administration or prior to start of subsequent anticancer treatment (whichever occurs first) ] [ Designated as safety issue: Yes ]
  • Prostate-specific antigen (PSA) response (30%, 50%, 90% and best) [ Time Frame: PSA level at baseline and every 4 weeks until disease progression (estimated up to 1 year) ] [ Designated as safety issue: No ]
  • Time to PSA progression [ Time Frame: PSA level at baseline and every 4 weeks until disease progression (estimated up to 1 year) ] [ Designated as safety issue: No ]
  • Radiographic progression-free survival (rPFS) [ Time Frame: Every 12 weeks until disease progression (estimated up to 1 year) ] [ Designated as safety issue: No ]
  • QL and pain response [ Time Frame: First 6 months of trial treatment ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: time from trial randomization to the date of death from any cause (estimated up to 4 years) ] [ Designated as safety issue: No ]

Estimated Enrollment: 192
Study Start Date: September 2012
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Orteronel and best supportive care
Arm A: 300mg Orteronel twice daily and best supportive care until occurrence of an event.
Drug: Orteronel
Other Name: TAK-700
Placebo Comparator: Placebo and best supportive care
Arm B: Placebo twice daily and best supportive care until occurrence of an event.
Drug: Placebo

  Show Detailed Description


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patient has given voluntary written informed consent
  • Male patient 18 years or older
  • WHO performance status of ≤2
  • Adenocarcinoma of the prostate
  • Castration resistance: tumor progression after orchiectomy or during treatment with GnRH analogues
  • Metastatic disease, radiographically documented (
  • Total testosterone ≤ 50 ng/dL
  • Non-progressive disease after docetaxel first-line treatment with a cumulative dose ≥ 300mg/m2

    • No evidence of progression on imaging according to PCWG2 and modified RECIST 1.1 criteria
    • PSA levels not elevated ≥ 25% AND at least 2 ng/mL above the nadir since start of docetaxel treatment
  • Non-surgically castrated patient agrees on ongoing use of GnRH analogues (agonists or antagonists) during the trial
  • PSA ≥ 2 ng/mL; Potassium ≥ 3.5 mmol/L; Neutrophils ≥ 1.5 x 109/L; Platelets ≥ 100 x 10x9/L
  • Normal kidney and liver function
  • Planned start of trial treatment 3 to 6 weeks after last docetaxel administration
  • Screening calculated ejection fraction of ≥ 50% or normal according to local standard by echocardiogram or by multiple gated acquisition (MUGA) scan.
  • Baseline QL questionnaire completed
  • Patient is able and willing to swallow study drug as whole tablet
  • Patient compliance and geographic proximity allow proper staging and follow-up
  • Patient agrees to practice effective barrier contraception or to completely abstain from intercourse

Exclusion Criteria:

  • Prior therapy with aminoglutethimide, ketoconazole, orteronel, abiraterone or other modern CYP17 inhibitors
  • Prior chemotherapy for prostate cancer within 12 months before enrollment except from docetaxel
  • Retreatment with docetaxel after interruption of > 5 weeks
  • Concurrent disease requiring higher doses of corticosteroid than the equivalent of 10 mg prednisone per day
  • Known hypersensitivity to trial drug or hypersensitivity to any of its components
  • Patient has received other investigational drugs within 30 days before enrollment
  • Presence of a small cell component in histological specimen
  • Radiotherapy within the last 2 weeks before expected start of the trial treatment
  • Known history of central nervous system (CNS) or spinal cord metastases
  • Current spinal cord compression
  • Diagnosed or treated for another malignancy within 2 years of registration, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, or any in situ malignancies
  • History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias of Grade ≥ 3 (NCI CTCAE version 4.0) or thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events) within 6 months prior to first dose of study drug. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed
  • New York Heart Association Class III or IV heart failure
  • ECG abnormalities of:

    • Q-wave infarction, unless identified ≥ 6 months prior to registration
    • QTc interval > 460 msec
  • Uncontrolled hypertension despite appropriate medical therapy
  • Likely inability (e.g. due to a psychiatric disorder) to understand information on trial related topics, to give informed consent, to comply with the protocol, to fill in QL forms and to cooperate fully with the investigator and site personnel
  • Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of orteronel
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01707966

Contact: Heike Kenner, PhD +41 31 389 91 81 Heike.Kenner@sakk.ch
Contact: Simona Berardi, PhD +41 31 389 93 86 Simona.Berardi@sakk.ch

Kantonspital Aarau Recruiting
Aarau, Switzerland, CH-5001
Contact: Philippe von Burg, MD    +41 62 838 59 94    philippe.vonburg@ksa.ch   
Principal Investigator: Philippe von Burg, MD         
Universitaetsspital Basel Recruiting
Basel, Switzerland, 4031
Contact: Frank Stenner, MD    +41 44 255 22 14    Frank.Stenner@usz.ch   
Principal Investigator: Frank Stenner, MD         
Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli Recruiting
Bellinzona, Switzerland, 6500
Contact: Enrico Roggero, MD       roggero@ticino.com   
Principal Investigator: Enrico Roggero, MD         
Inselspital Bern Recruiting
Bern, Switzerland, CH-3010
Contact: Adrian Ochsenbein, Prof.    +41 31 632 81 69    adrian.ochsenbein@sec.insel.ch   
Principal Investigator: Adrian Ochsenbein, MD         
Kantonsspital Graubuenden Recruiting
Chur, Switzerland, 7000
Contact: Richard Cathomas, MD    +41 81 256 66 95    richard.cathomas@ksgr.ch   
Principal Investigator: Richard Cathomas, MD         
Kantonsspital Freiburg Recruiting
Freiburg, Switzerland, 1708
Contact: Daniel Betticher, MD    41-26-426-7243    betticherd@h-fr.ch   
Principal Investigator: Daniel Betticher, Prof         
Hôpitaux Universitaires de Genève HUG Recruiting
Geneva 14, Switzerland, 1211
Contact: Marie-Laure Amram, MD    +41 22 372 98 76    Marie-Laure.Amram@hcuge.ch   
Principal Investigator: Marie-Laure Amram, MD         
Centre Hospitalier Universitaire Vaudois CHUV Recruiting
Lausanne, Switzerland, CH-1011
Contact: Dominik Berthold, MD    +41 21 314 80 83    Dominik.Berthold@chuv.ch   
Principal Investigator: Dominik Berthold, MD         
Kantonsspital Luzern Recruiting
Luzern, Switzerland, 6000
Contact: Ralph Winterhalder, MD    +41 41 205 58 75    ralph.winterhalder@ksl.ch   
Principal Investigator: Ralph Winterhalder, MD         
Kantonsspital Muensterlingen Recruiting
Muensterlingen, Switzerland, 8596
Contact: Roman Inauen, MD    +41 71 686 11 11    roman.inauen@stgag.ch   
Principal Investigator: Roman Inauen, MD         
Spital Männedorf Recruiting
Männedorf, Switzerland, 8708
Contact: Cornelia Dröge, MD    +41 44 922 30 00    c.droege@spitalmaennedorf.ch   
Principal Investigator: Cornelia Dröge, MD         
Kantonsspital St. Gallen Recruiting
St. Gallen, Switzerland, 9007
Contact: Silke Gillessen, Prof    +41 71 494 10 92    silke.gillessen@kssg.ch   
Principal Investigator: Silke Gillessen, Prof         
SpitalSTS AG Simmental-Thun-Saanenland Recruiting
Thun, Switzerland, 3600
Contact: Daniel Rauch    +41 33 226 26 45    daniel.rauch@spitalstsag.ch   
Principal Investigator: Daniel Rauch, MD         
Kantonsspital Winterthur Recruiting
Winterthur, Switzerland, 8401
Contact: Natalie Fischer, MD    +41 052 266 40 87    natalie.fischer@ksw.ch   
Principal Investigator: Natalie Fischer, MD         
UniversitaetsSpital Zuerich Recruiting
Zurich, Switzerland, 8091
Contact: Axel Mischo, MD    +41 44 255 22 14    axel.mischo@usz.ch   
Principal Investigator: Axel Mischo, MD         
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Study Chair: Richard Cathomas, MD Kantonsspital Graubünden
Study Chair: Silke Gillessen, Prof Cantonal Hospital of St. Gallen
  More Information

No publications provided

Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT01707966     History of Changes
Other Study ID Numbers: SAKK 08/11, 2011-002965-39
Study First Received: September 13, 2012
Last Updated: April 22, 2014
Health Authority: Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Swiss Group for Clinical Cancer Research:
adenocarcinoma of the prostate
metastatic castration-resistant prostate cancer
maintenance therapy

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 19, 2014