Crizotinib Efficacy In Non-Small Cell Lung Cancer Patients With Anaplastic Lymphoma Kinase Translocation
This is an exploratory study in patients with locally advanced or metastatic Non-small cell lung cancer. Patients who are eligible to apply for Extended Access Program of crizotinib must have ALK translocation detected by RT-PCR, IHC or FISH analyses methods.
Non-small Cell Lung Cancer(NSCLC)
|Study Design:||Time Perspective: Prospective|
|Official Title:||An Exploratory Study Of Crizotinib Efficacy In Non-Small Cell Lung Cancer Patients With Anaplastic Lymphoma Kinase Translocation Determined By Different Molecular Diagnostic Methods|
- Overall response rate in patients with positive ALK determined from different molecular analysis methods. [ Time Frame: It is defined as the time from day 1 of crizotinib to disease progression or patient's death. ] [ Designated as safety issue: No ]
- Progression-free survival (PFS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Overall survival (OS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
Blood and tumor tissue are being collected during the course of this study, to assess the safety and tolerability and spectrum of side effects of the study drug. However, it is possible that after completion of all study-related analyses, some volume of samples may remain. These left-over samples could be a valuable resource for future research.
Before any left-over samples can be used for any research other than that specified in the protocol, patient must sign an additional future use consent from indicating they give their permission for these samples to be used in future research. By signing the main consent form, patients are only giving their permission to use their samples for the study related procedures.
|Study Start Date:||June 2012|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
This is an exploratory non-randomized study in patients with locally advanced or metastatic NSCLC. Patients who are eligible to apply for Extended Access Program of crizotinib must have ALK translocation detected by RT-PCR, IHC or FISH analyses methods. Patients who failed and progressed through at least one line of platinum containing chemotherapy and who are older than 70 years old with failure of chemotherapy will be eligible for this study. We will screen EML4-ALK fusion gene by RT-PCR (HotSart Taq Master Mix Kits, Qiaqen) from patients' malignant pleural effusions and the detail was described in previous study. We will also use IHC analyses (5A4 monoclonal antibody, Novocastra) to screen ALK protein expression in patients' FFPE tumor sections. We will further do FISH analysis by using commercial Vysis LSI ALK Dual Color, Break Apart Rearrangement Probe (2p23) (Abott Molecular Inc., Des Plaines, IL) to detect ALK rearrangement in positive screening tumors. Samples are deemed to be FISH-positive if more than 15% of 50 scored tumor cells had split ALK 5' and 3' probe signals or had isolated 3' signals. Patients who have ALK rearrangement determined in any of 3 molecular analyses methods and apply for crizotinib will receive 250mg of crizotinib twice daily until disease progression, unacceptable toxicities or the withdrawal of consent is noted.
Patients will be monitored carefully for the development of adverse experiences. Adverse experiences will be evaluated according to criteria outlined in the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Patients will also be monitored for clinical and/or radiographic evidence of disease progression according to RECIST 1.1.
The primary endpoint of the study is overall response rate in patients with positive ALK determined from different molecular analysis methods. The secondary endpoint included overall response in specific subsets of patients, progression-free survival (PFS), and overall survival (OS) at 1 year. PFS is defined as the time from day 1 of crizotinib to disease progression or patient's death. OS was defined as the time from day 1 of crizotinib treatment to patient's death.
During the treatment, patients will have safety measurements performed at specified time points. Disease response will be assessed during the study by radiographic (e.g., CT or MRI), and clinical (e.g., physical examination) evaluations, if applicable. Overall tumor response will be assessed at the designated time points (every 12 weeks, using Response Evaluation Criteria in Solid Tumors (RECIST, Version 1.1). The crizotinib treatment could be continued after RECIST-defined disease progression if clinical benefit is still noted by primary physician.
|Department of Oncology, National Taiwan University Hospital|
|Taipei, Taiwan, 100|
|Principal Investigator:||James Chih-Hsin Yang, MD, PhD||National Taiwan University Hospital|