A Phase IV Multicenter Trial to Evaluate the Resistance Mechanisms and Real-world Pharmacoeconomics of Crizotinib and Its Companion Diagnostic Test in Advanced ALK-positive Non-small Cell Lung Cancer (NSCLC) Patients
试验速览
- 阶段
- 不适用
- 入组人数
- 29
- 试验地点
- 8
- 主要终点
- The pharmacoeconomic impact of using personalized medicine for the treatment of ALK+ lung cancer.
研究概览
简要总结
This is a phase IV multicenter trial to evaluate the mechanisms of resistance and pharmacoeconomic (PE) impact of crizotinib and its companion diagnostic test used in a real-life setting in advanced ALK-positive non-small cell lung cancer (NSCLC) patients.
The study will address two anticipated issues surrounding personalized medicine and treatment with crizotinib:
- it will enable real-life Heath Economics and Outcome Research (HEOR)
- it will validate and/or identify new blood-based or tissue-based biomarkers of resistance to crizotinib.
At least 30 patients will be recruited in Quebec and Ontario for the PE study. Patients will be asked to complete quality-of-life questionnaires at regular intervals in a real-life setting of treatment with crizotinib.
Approximately 25 patients will be recruited to the biomarker sub-study in Quebec to understand resistance mechanisms of crizotinib. In these patients, a biopsy from any accessible metastatic lesion will be obtained when the patient is no longer responding to treatment, as well as blood sampling during regular treatment visits.
详细描述
This is a phase IV multicenter trial to evaluate the mechanisms of resistance and pharmacoeconomic (PE) impact of crizotinib and its companion diagnostic test used in a real-life setting in advanced ALK-positive non-small cell lung cancer (NSCLC) patients.
NSCLC represent 80% of all new cases of lung cancer. One molecular subtype of NSCLC is the ALK-positive subtype. The anaplastic lymphoma kinase (ALK) is a transmembrane receptor tyrosine kinase. Activation of ALK occurs through the formation of gene fusions and in NSCLC, the gene fusion partner for ALK is primarily EML4. The resulting fusion protein is capable of activating the ALK kinase domain, leading to cell growth. The estimated prevalence for ALK rearrangements in NSCLC is 3-5%, and is more commonly found amongst patients with adenocarcinoma histology, in never smokers and in those who are known to be wild type for EGFR and KRAS.
Crizotinib is a potent inhibitor of ALK and is approved for the treatment of advanced ALK+ NSCLC patients. This is an example of personalized medicine, where patients are selected for treatment based upon a molecular assay, and are provided a specific therapy (crizotinib) for their disease. The pharmacoeconomic impact of using genetic information in early treatment decisions in NSCLC has not been determined. Despite the benefits of crizotinib, some patients do not respond to treatment and most patients will eventually develop resistance. To date, it is unclear why some rare patients do not respond to treatment and the resistance mechanisms of crizotinib have not been fully elucidated.
The study will address two anticipated issues surrounding personalized medicine and treatment with crizotinib:
- it will enable real-life Heath Economics and Outcome Research (HEOR)
- it will validate and/or identify new blood-based or tissue-based biomarkers of resistance to crizotinib.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically confirmed locally advanced or metastatic NSCLC
- •Presence of the ALK-fusion oncogene (ALK+) as determined using a validated testing platform
- •Measurable disease according to RECIST v. 1.1
- •Planned or ongoing treatment with crizotinib
- •Signed and dated IRB-approved informed consent document
- •Ability to read and understand English or French
- •18 years of age or older
排除标准
- •Acquired immunodeficiency syndrome (AIDS-related illnesses) or known HIV disease.
- •Unwilling to provide consent for genetic studies of the tumor, whole blood, or plasma specimens.
结局指标
主要结局
The pharmacoeconomic impact of using personalized medicine for the treatment of ALK+ lung cancer.
时间窗: From the date of registration until date of death from any cause, assessed up to 60 months.
Pharmacoeconomic impact (cost-effectiveness and cost utility) will be evaluated by questionnaires completed by the patient and caregiver. These include quality of life, health resource utilization, work productivity and activity impairment, and health questionnaires
次要结局
- Number of participants with adverse events related to the biopsy procedure.(Up to 4 years.)
- Change in blood-based biomarkers of response to crizotinib.(From the date of registration until the date of treatment discontinuation, an expected average of 24 months.)
- Type of resistance mechanisms identified in crizotinib-resistant tumors(At progression of disease, an expected average of 24 months.)
研究者
Dr. Jason Agulnik
Principal Investigator
Jewish General Hospital