A Randomised, Double-Blind, Placebo-Controlled, Multicentre Phase II Study to Compare the Efficacy, Safety and Tolerability of Olaparib Versus Placebo When Given in Addition to Abiraterone Treatment in Patients With Metastatic Castrate-Resistant Prostate Cancer Who Have Received Prior Chemotherapy Containing Docetaxel

AstraZeneca AB0 个研究点目标入组 158 人2014年7月21日

概览

阶段: 1 期
干预措施: 未指定
疾病 / 适应症: 未指定
发起方: AstraZeneca AB
入组人数: 158
状态: 进行中（未招募）
最后更新: 2年前

概览研究者入排标准结局指标相似试验

概览

简要总结

暂无简介。

注册库

who.int

开始日期

2014年7月21日

结束日期

2023年8月24日

最后更新

2年前

研究类型

Interventional clinical trial of medicinal product

性别

Male

研究者

发起方

AstraZeneca AB

入排标准

入选标准

•1\. Provision of signed and dated written informed consent prior to any study specific procedures. 2\. Male aged 18 years and older. 3\. Histologically or cytologically proven diagnosis of prostate cancer. 4\. Candidate for abiraterone therapy with documented evidence of metastatic castration\-resistant prostate cancer. Metastatic status is defined as at least one documented metastatic lesion on either bone scan or CT/MRI scan. Castration resistant prostate cancer is defined as rising PSA or other signs of disease progression despite treatment with androgen deprivation therapy and the presence of a castrate level of testosterone (\=50 ng/dL). 5\. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 with no deterioration over the previous 2 weeks. 6\. Patients must have a life expectancy \=12 weeks. 7\. Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations, and completing PRO instruments. 8\. Patients must be on a stable concomitant medication regimen, defined as no changes in medication or in dose within 2 weeks prior to start of olaparib dosing, except for bisphosphonates, denosumab and corticosteroids, which should be stable for at least 4 weeks prior to start of olaparib dosing. 9\. For the randomised phase only, patients must have received chemotherapy in the form of docetaxel treatment for metastatic castration\-resistant prostate cancer. Note: patients who discontinued docetaxel for toxicity reasons and without completing the full course will still be eligible to enter this study provided they received at least 2 cycles of chemotherapy. Provide informed consent for the pharmacogenetic sampling and analyses.
•Are the trial subjects under 18? no
•Number of subjects for this age range:
•F.1\.2 Adults (18\-64 years) yes
•F.1\.2\.1 Number of subjects for this age range 70
•F.1\.3 Elderly (\>\=65 years) yes
•F.1\.3\.1 Number of subjects for this age range 100

排除标准

•1\. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff, its agents and/or staff at the study site). 2\. Previous treatment in the present study. 3\. Treatment with any of the following:\- Previous exposure to any 2nd generation anti\-hormonal including abiraterone and enzalutamide\- More than 2 prior courses of chemotherapy for metastatic prostate cancer\- Previous use of immunotherapy or radium\-223 for the treatment of metastatic prostate cancer\- Any investigational agents or study drugs from a previous clinical study within 30 days of the first dose of study treatment;\- Any previous exposure to a CYP17 (17a\-hydroxylase/C17,20\-lyase) inhibitor;\- Substrates of CYP2D6 with a narrow therapeutic index (eg, thioridazine);\- Potent inhibitors or inducers of CYP3A4 within 2 weeks before the first dose of study treatment (3 weeks for St John’s Wort).\- Any previous treatment with a PARP inhibitor, including olaparib. 4\. With the exception of alopecia or toxicities related to the use of gonadotropinreleasing hormone agonists, any unresolved toxicities from prior therapy greater than CTCAE Grade 2 at the time of starting study treatment. 5\. Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment. 6\. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required. 7\. Any of the following cardiac criteria:\- Mean resting QTc \>470 msec obtained from 3 ECGs\- Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG eg, complete left bundle branch block, third degree heart block\- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval. 8\. Other malignancy within the last 5 years except: adequately treated non\-melanoma skin cancer or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for \=5 years. 9\. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:\- Absolute neutrophil count (ANC) \<1\.5 x 109/L\- Platelet count \<100 x 109/L\- Haemoglobin (Hb) \<100 g/L\- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)\> 2\.5 x upper limit of normal (ULN) if no demonstrable liver metastases or\> 5 x ULN in the presence of liver metastases\- Total bilirubin \>1\.5 x ULN if no liver metastases or \>3 x ULN in the presence of liver metastases (except in the case of Gilbert’s disease)\- Creatinine \>1\.5 x ULN concurrent with creatinine clearance \<50 mL/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is \>1\.5 x ULN\- If bone metastases are present and liver function is otherwise considered adequate by the Investigator then elevated alkaline phosphatase (ALP) will not exclude the patient. 10\. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bo