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

Trial details

Who runs it

Swiss Cancer Institute

Trial code

NCT02053311

Record updated

2018. július 30.

Original description

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.Read full original descriptionShow less

Orteronel Maintenance Therapy in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC) Previously Treated With Novel Hormonal Agents and Non-progressive Disease After Treatment With a Taxane: A Multicentre Randomized Double-blind Placebo-controlled Phase III Trial

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.

Inclusion: 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care; Male patient 18 years or older; WHO performance status of ≤2; Adenocarcinoma of the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); Estimated creatinine clearance using the Cockcroft-Gault formula > 40 mL/minute; Planned start of trial treatment 2 to 8 weeks after last taxane dose; Calculated ejection fraction of ≥ 50% or normal according to local standard by echocardiogram or by multiple gated acquisition (MUGA) scan; Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before expected start of treatment; Patient is able and willing to complete 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, even if surgically sterilized (i.e., status post vasectomy); agrees to practice effective barrier contraception during the entire study treatment period and for 4 months after the last dose of study drug, or; agrees to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient.

Exclusion: Prior therapy with aminoglutethimide and/or ketoconazole; Prior chemotherapy for prostate cancer within 12 months before enrollment except from chemotherapy with a taxane; Concurrent disease requiring higher doses of corticosteroid than the equivalent of 10 mg prednisone per day; Concurrent treatment with other experimental drugs or treatment in a clinical trial within 30 days prior to trial entry; Radiotherapy within the last 2 weeks before expected start of the trial treatment; 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; Retreatment with a taxane for metastatic prostate cancer after interruption of > 8 weeks; Known allergy and/or hypersensitivity and/or any known grade 4 toxicity to modern CYP17 inhibitors and to any of their components and GnRH; Known history of central nervous system (CNS) or spinal cord metastases; New York Heart Association Class III or IV heart failure; Uncontrolled hypertension despite appropriate medical therapy (systolic blood pressure > 160 mm Hg or diastolic blood pressure > 90 mmHg) at 2 separate measurements no more than 60 minutes apart during the Screening visit); 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 illness that could, in the investigator's opinion, potentially interfere with participation in this study; Any psychological, familial, sociological or geographical condition potentially hampering compliance with the trial protocol and follow-up; ECG abnormalities of:; Q-wave infarction, unless identified ≥ 6 months prior to registration; QTc interval > 460 msec; Presence of a small cell component in histological specimen; Current spinal cord compression.

ClinicalTrials.gov NCT02053311