A Phase II Study Evaluating the Efficacy of Enzalutamide and the Role of ARv7 in Metastatic Castration Resistant Prostate Cancer (mCRPC) Patients With Visceral Disease. (EXCALIBUR)
2021年4月23日 更新者:Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Open label, single arm, phase II multicentre study designed to determine the clinical benefit, as measured by 3-months disease control rate (DCR) provided by enzalutamide in metastatic Castration Resistant Prostate Cancer patients with at least one visceral site involvement.
研究概览
研究类型
介入性
注册 (实际的)
68
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习地点
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Milan、意大利、20133
- Elena Verzoni
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参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
男性
描述
Inclusion Criteria:
- Age > 18
- ECOG PS 0-1-2
- Biopsy (primary tumour or metastases) confirming the diagnosis of prostate adenocarcinoma
- Documented measurable metastatic visceral disease (according to RECIST 1.1 criteria) considering metastases in lung or liver or extraregional lymphnodes
- Written informed consent
- Platelets > or = 100 x109/L; haemoglobin > or = 9 g/dl; neutrophils > or 1.5 x 109/L
- Bilirubin < or = 2 mg/dl, AST and ALT < or = 2.5 times the UNL or < or = 5 times UNL for pts with liver metastases; serum albumin > or = the LNL
- Patients of childbearing age should use contraceptive methods
- Life expectancy > 3 months
- Able to swallow the study drug and comply with study requirements;
- Willing and able to give informed consent.
- Ongoing androgen deprivation therapy with a GnRH analogue or orchiectomy (i.e., surgical or medical castration);
- Patients may have received previous therapy including chemotherapy (docetaxel) last cycle must be received 3 weeks before start of experimental treatment. Hormonal treatment containing bicalutamide must be interrupted 2 weeks before start of study therapy
- Previous radiotherapy (prostate and/or bone) is accepted but must be interrupted 3 weeks before start of experimental treatment.
- Serum testosterone level < 1.7 nmol/L (50 ng/dL) at the Screening visit
Progressive disease by PSA or imaging in the setting of medical or surgical castration. Disease progression for study entry is defined as one or more of the following three criteria (according with PCWG2):
- PSA progression defined by a minimum of three rising PSA levels with an interval of ≥ 1 week between each determination. The PSA value at the Screening visit should be ≥ 2 g/L (2 ng/ml); if the third PSA value is less than second PSA, a fourth PSA must be repeated and if it the value is higher than second must be considered as disease
- Soft tissue/visceral disease progression defined by RECIST 1.1;
- Bone disease progression defined by two or more new lesions on bone scan.
Exclusion Criteria:
- Severe, concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment;
- Metastases in the brain or active epidural disease;
- History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer;
- History of seizure, including any febrile seizure, loss of consciousness, or transient ischemia attack within 12 months of enrollment (Day 1 visit), or any condition that may pre-dispose to seizure (e.g., prior stroke, head trauma with loss of consciousness requiring hospitalization);
- Clinically significant cardiovascular disease including: Myocardial infarction within 6 months; Uncontrolled angina within 3 months; Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patients with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within 3 months results in a left ventricular ejection fraction that is ≥ 45%;
- Diagnosed or suspected congenital long QT syndrome;
- History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes);
- Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer within last 3 months);
- Major surgery within 4 weeks prior to enrollment (Day 1 visit);
- Prior treatment with abiraterone acetate;
- Participation in a clinical trial about an experimental anti-androgen agent (eg. ARN-509, ODM-201, VT-464, except for placebo arm);
- Treatment (concomitant or in the previous 2 weeks) with anti-androgens (eg. Bicalutamide, nilutamide, flutamide) or 5-a reductase inhibitors (eg. finasteride, dutasteride).
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Enzalutamide
All subjects will receive open label enzalutamide 160 mg (4 x 40 mg capsules), orally once daily.
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Enzalutamide 160 mg (4 x 40 mg capsules), orally once daily
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Disease Control Rate (DCR)
大体时间:3 months
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To determine the clinical benefit, as measured by 3 months disease control rate (DCR) provided by enzalutamide in mCRPC patients with visceral disease.
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3 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Safety of the treatment per NCI-CTCA v. 4.0
大体时间:2 years
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To determine the safety of the treatment according to NCI-CTCA v. 4.0
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2 years
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Quality of life by EQ-5D-5L e FACT-P
大体时间:2 years
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To evaluate quality of life as assessed by EQ-5D-5L e FACT-P questionnaire
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2 years
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Pain assessment
大体时间:2 years
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To evaluate pain as assessed by BPI-SF questionnaire
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2 years
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员:Elena Verzoni, MD、Fondazione IRCCS Istituto Nazionale Tumori Milano
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
- Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.
- Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, Mason M, Matveev V, Wiegel T, Zattoni F, Mottet N; European Association of Urology. EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2014 Feb;65(2):467-79. doi: 10.1016/j.eururo.2013.11.002. Epub 2013 Nov 12.
- Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ, Flaig TW, Flechon A, Mainwaring P, Fleming M, Hainsworth JD, Hirmand M, Selby B, Seely L, de Bono JS; AFFIRM Investigators. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012 Sep 27;367(13):1187-97. doi: 10.1056/NEJMoa1207506. Epub 2012 Aug 15.
- Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC, Chen Y, Mohammad TA, Chen Y, Fedor HL, Lotan TL, Zheng Q, De Marzo AM, Isaacs JT, Isaacs WB, Nadal R, Paller CJ, Denmeade SR, Carducci MA, Eisenberger MA, Luo J. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med. 2014 Sep 11;371(11):1028-38. doi: 10.1056/NEJMoa1315815. Epub 2014 Sep 3.
- Astellas Pharma Ltd. Xtandi (enzalutamide) 40mg soft capsules. Summary of Product Characteristics. 26 June 2013.
- Ahmed M, Li LC. Adaptation and clonal selection models of castration-resistant prostate cancer: current perspective. Int J Urol. 2013 Apr;20(4):362-71. doi: 10.1111/iju.12005. Epub 2012 Nov 19.
- Arlen PM, Bianco F, Dahut WL, D'Amico A, Figg WD, Freedland SJ, Gulley JL, Kantoff PW, Kattan MW, Lee A, Regan MM, Sartor O; Prostate Specific Antigen Working Group. Prostate Specific Antigen Working Group guidelines on prostate specific antigen doubling time. J Urol. 2008 Jun;179(6):2181-5; discussion 2185-6. doi: 10.1016/j.juro.2008.01.099. Epub 2008 Apr 18.
- Beer TM, Tombal B. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014 Oct 30;371(18):1755-6. doi: 10.1056/NEJMc1410239. No abstract available.
- Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010 Mar;46(4):765-81. doi: 10.1016/j.ejca.2009.12.014. Epub 2010 Jan 29.
- Fitzpatrick JM, de Wit R. Taxane mechanisms of action: potential implications for treatment sequencing in metastatic castration-resistant prostate cancer. Eur Urol. 2014 Jun;65(6):1198-204. doi: 10.1016/j.eururo.2013.07.022. Epub 2013 Jul 25.
- Horwich A, Parker C, de Reijke T, Kataja V; ESMO Guidelines Working Group. Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013 Oct;24 Suppl 6:vi106-14. doi: 10.1093/annonc/mdt208. Epub 2013 Jun 27. No abstract available.
- Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941. J Urol. 2002 Feb;167(2 Pt 2):948-51; discussion 952. No abstract available.
- Kuczynski EA, Sargent DJ, Grothey A, Kerbel RS. Drug rechallenge and treatment beyond progression--implications for drug resistance. Nat Rev Clin Oncol. 2013 Oct;10(10):571-87. doi: 10.1038/nrclinonc.2013.158. Epub 2013 Sep 3.
- Merseburger AS, Bellmunt J, Jenkins C, Parker C, Fitzpatrick JM; European Treatment Practices Group. Perspectives on treatment of metastatic castration-resistant prostate cancer. Oncologist. 2013;18(5):558-67. doi: 10.1634/theoncologist.2012-0478. Epub 2013 May 13. Erratum In: Oncologist. 2013;18(6):775. Oncologist. 2013;18(8):971.
- Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, Efstathiou E, Pantuck A, Winquist E, Higano CS, Taplin ME, Park Y, Kheoh T, Griffin T, Scher HI, Rathkopf DE; COU-AA-302 Investigators. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013 Jan 10;368(2):138-48. doi: 10.1056/NEJMoa1209096. Epub 2012 Dec 10. Erratum In: N Engl J Med. 2013 Feb 7;368(6):584.
- Ryan CJ, Tindall DJ. Androgen receptor rediscovered: the new biology and targeting the androgen receptor therapeutically. J Clin Oncol. 2011 Sep 20;29(27):3651-8. doi: 10.1200/JCO.2011.35.2005. Epub 2011 Aug 22.
- Scher HI, Beer TM, Higano CS, Anand A, Taplin ME, Efstathiou E, Rathkopf D, Shelkey J, Yu EY, Alumkal J, Hung D, Hirmand M, Seely L, Morris MJ, Danila DC, Humm J, Larson S, Fleisher M, Sawyers CL; Prostate Cancer Foundation/Department of Defense Prostate Cancer Clinical Trials Consortium. Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study. Lancet. 2010 Apr 24;375(9724):1437-46. doi: 10.1016/S0140-6736(10)60172-9. Epub 2010 Apr 14.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2017年3月16日
初级完成 (实际的)
2021年4月23日
研究完成 (实际的)
2021年4月23日
研究注册日期
首次提交
2017年3月31日
首先提交符合 QC 标准的
2017年4月5日
首次发布 (实际的)
2017年4月6日
研究记录更新
最后更新发布 (实际的)
2021年4月26日
上次提交的符合 QC 标准的更新
2021年4月23日
最后验证
2021年4月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
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