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

NCT01707966 | Completed Phase 3

• 2 other identifiers: SAKK 08/112011-002965-39
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

Prostate Cancer

Keywords

adenocarcinoma of the prostate; metastatic castration-resistant prostate cancer; maintenance therapy; orteronel; TAK-700

Outcome Measures

Primary Outcomes (1)

• Event free survival (EFS)

  At baseline; every 4 weeks until disease progression (estimated up to 1 year)

Secondary Outcomes (6)

• Adverse events (AEs)

  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)

• Prostate-specific antigen (PSA) response (30%, 50%, 90% and best)

  PSA level at baseline and every 4 weeks until disease progression (estimated up to 1 year)

• Time to PSA progression

  PSA level at baseline and every 4 weeks until disease progression (estimated up to 1 year)

• Radiographic progression-free survival (rPFS)

  Every 12 weeks until disease progression (estimated up to 1 year)

• QL and pain response

  First 6 months of trial treatment

Study Arms (2)

Orteronel and best supportive care

EXPERIMENTAL

Arm A: 300mg Orteronel twice daily and best supportive care until occurrence of an event.

Drug: Orteronel

Placebo and best supportive care

PLACEBO COMPARATOR

Arm B: Placebo twice daily and best supportive care until occurrence of an event.

Drug: Placebo

Interventions

Orteronel DRUG

Also known as: TAK-700

Orteronel and best supportive care

Placebo DRUG

Placebo and best supportive care

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (15)

Kantonspital Aarau

Aarau, CH-5001, Switzerland

Location

Universitaetsspital Basel

Basel, 4031, Switzerland

Location

Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Kantonsspital Graubuenden

Chur, 7000, Switzerland

Location

Kantonsspital Freiburg

Fribourg, 1708, Switzerland

Location

Hôpitaux Universitaires de Genève HUG

Geneva, 1211, Switzerland

Location

Centre Hospitalier Universitaire Vaudois CHUV

Lausanne, CH-1011, Switzerland

Location

Kantonsspital Luzern

Lucerne, 6000, Switzerland

Location

Spital Männedorf

Männedorf, 8708, Switzerland

Location

Kantonsspital Muensterlingen

Münsterlingen, 8596, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

SpitalSTS AG Simmental-Thun-Saanenland

Thun, 3600, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, 8091, Switzerland

Location

Related Publications (1)

• Cathomas R, Crabb SJ, Mark M, Winterhalder R, Rothermundt C, Elliott T, von Burg P, Kenner H, Hayoz S, Vilei SB, Rauch D, Roggero E, Mohaupt MG, Bernhard J, Manetsch G, Gillessen S; Swiss Group for Clinical Cancer Research SAKK. Orteronel Switch Maintenance Therapy in Metastatic Castration Resistant Prostate Cancer After First-Line Docetaxel: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial (SAKK 08/11). Prostate. 2016 Dec;76(16):1519-1527. doi: 10.1002/pros.23236. Epub 2016 Jul 25.

  PMID: 27457964 RESULT

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

orteronel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Richard Cathomas, MD

  Kantonsspital Graubünden

  STUDY CHAIR

• Silke Gillessen, Prof

  Cantonal Hospital of St. Gallen

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2012
• First Posted: October 16, 2012
• Study Start: September 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: July 1, 2016
• Last Updated: May 15, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

CH (15)