Orteronel Maintenance Therapy in Patients With mCRPC Previously Treated With Novel Hormonal Agents

NCT02053311 | Withdrawn Phase 3

• 2 other identifiers: SAKK 08/132013-004912-23
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 7

Brief Summary

The main object of this multicenter, randomized, double-blind, placebo-controlled phase III trial is to assess impact of maintenance of orteronel on disease progression and hence on quality of life of patients with metastatic castration resistant prostate cancer pretreated with novel hormonal agents who have non-progressive disease after chemotherapy with a taxane.

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

  The primary endpoint of the trial is EFS. An event is defined as ONE of the following: * death from any cause * the presence of radiographic progression AND symptomatic/clinical progression * the presence of radiographic progression AND PSA progression * the presence of symptomatic/clinical progression AND PSA progression

  5 months

Secondary Outcomes (7)

• 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)

• Overall survival (OS)

  time from trial randomization to the date of death from any cause (estimated up to 4 years)

Study Arms (2)

Arm A: Orteronel

ACTIVE COMPARATOR

300mg orteronel twice daily and best supportive care until disease progression

Drug: Orteronel

Arm B: Placebo

ACTIVE COMPARATOR

Placebo twice daily and best supportive care until disease progression

Drug: Placebo

Interventions

Orteronel DRUG

300mg orteronel

Also known as: TAK-700

Arm A: Orteronel

Placebo DRUG

Placebo

Arm B: Placebo

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 before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Male patient 18 years or older
• WHO performance status of ≤2
• Adenocarcinoma of the prostate, histologically or cytologically confirmed
• Castration resistance: tumor progression after orchiectomy or during treatment with GnRH analogues (agonists or antagonists)
• Metastatic disease, radiographically documented (CT/MRI, bone scan)
• Total testosterone ≤ 50 ng/dL (≤ 1.7 nmol/L)
• Treatment with a CYP17 inhibitor or a novel antiandrogen (such as enzalutamide, ODM-201, ARN-509, but not restricted to) or the combination of both agents) for at least 8 weeks prior to one line of a taxane based chemotherapy.
• No evidence of disease progression after chemotherapy with docetaxel (cumulative dose of ≥ 450 mg/m2 or total dose ≥900mg) or cabazitaxel (cumulative dose of ≥150 mg/m2 or total dose ≥300mg)
• Non-surgically castrated patient agrees on ongoing use of GnRH analogues (agonists or antagonists) during the trial
• Laboratory values as specified below
• Potassium ≥ 3.5 mmol/L
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L and platelet count ≥ 100 x 109/L
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
• Total bilirubin ≤ 1.5 x ULN (except for patient with Gilbert's disease ≤ 5.0 x ULN)

You may not qualify if:

• Prior therapy with aminoglutethimide and/or ketoconazole
• Prior chemotherapy for prostate cancer within 12 months before enrollment except from chemotherapy with a taxane
• Retreatment with a taxane for metastatic prostate cancer after interruption of \> 8 weeks
• Concurrent disease requiring higher doses of corticosteroid than the equivalent of 10 mg prednisone per day
• Known allergy and/or hypersensitivity and/or any known grade 4 toxicity to modern CYP17 inhibitors and to any of their components and GnRH
• Concurrent treatment with other experimental drugs or treatment in a clinical trial within 30 days prior to trial entry
• 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
• Diagnosis of or treatment for another systemic malignancy within 2 years before registration or patient previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any time are not excluded if they have undergone complete resection.
• 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) or any other cardiac condition (e.g. pericardial effusion, restrictive cardiomyopathy) within 6 months before the 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 (7)

Kantonsspital Baden

Baden, CH-5404, Switzerland

Location

Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Kantonsspital Luzern

Luzerne, CH-6000, Switzerland

Location

Kantonsspital Muensterlingen

Münsterlingen, 8596, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

SpitalSTS AG Simmental-Thun-Saanenland

Thun, 3600, Switzerland

Location

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: January 29, 2014
• First Posted: February 3, 2014
• Study Start: August 19, 2014
• Primary Completion: August 19, 2014
• Study Completion (Estimated): August 19, 2034
• Last Updated: July 30, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

CH (7)