Clinical trial NCT02041468: Study to Evaluate Resistance Mechanisms and Real-world Pharmacoeconomics of Crizotinib in NSCLC Patients
Official title: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Non-small Cell Lung Cancer Metastatic
Keywords: ALK-positive
Lead sponsor: Jewish General Hospital
Sponsor class: OTHER
Collaborators: name: Pfizer
name: Quebec Clinical Research Organization in Cancer
name: PeriPharm
name: Personalized Medicine Partnership for Cancer
First posted: 2014-01-22
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) found positive for ALK mutation from participating hospitals in Quebec.

Brief summary: 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.

Detailed description: 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: The pharmacoeconomic impact of using personalized medicine for the treatment of ALK+ lung cancer.
timeFrame: From the date of registration until date of death from any cause, assessed up to 60 months.
Secondary outcomes:
measure: Type of resistance mechanisms identified in crizotinib-resistant tumors
timeFrame: At progression of disease, an expected average of 24 months.
measure: Change in blood-based biomarkers of response to crizotinib.
timeFrame: From the date of registration until the date of treatment discontinuation, an expected average of 24 months.
measure: Number of participants with adverse events related to the biopsy procedure.
timeFrame: Up to 4 years.
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center (JGH, St-Mary's, MGH, RVH)
state: Quebec
city: Montreal
country: Canada
facility: Centre hospitalier de l'Université de Montréal
state: Quebec
city: Montréal
country: Canada
facility: Hôpital du Sacré-Coeur de Montréal
state: Quebec
city: Rimouski
country: Canada
facility: CSSS Rimouski
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke
state: Quebec
city: Quebec
country: Canada
facility: Institut Universitaire de cardiologie et de pneumonologie
Study officials:
affiliation: Jewish General Hospital
name: Jason Agulnik, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Jewish General Hospital
name: Victor Cohen, MD
role: PRINCIPAL_INVESTIGATOR
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citation: Couetoux du Tertre M, Marques M, McNamara S, Gambaro K, Hoffert C, Tremblay L, Bouchard N, Diaconescu R, Blais N, Couture C, Pelsser V, Wang H, McIntosh L, Hindie V, Parent S, Cortes L, Breton YA, Pottiez G, Croteau P, Higenell V, Izzi L, Spatz A, Cohen V, Batist G, Agulnik J. Discovery of a putative blood-based protein signature associated with response to ALK tyrosine kinase inhibition. Clin Proteomics. 2020 Feb 7;17:5. doi: 10.1186/s12014-020-9269-6. eCollection 2020.