Study to Evaluate Resistance Mechanisms and Real-world Pharmacoeconomics of Crizotinib in NSCLC Patients

NCT ID: NCT02041468

Last Updated: 2017-08-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

29 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-01-31

Study Completion Date

2018-06-30

Brief Summary

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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

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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.

Conditions

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Non-small Cell Lung Cancer Metastatic

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Pharmacoeconomic main study

Patients from Quebec and Ontario (first or second line treatment)

No interventions assigned to this group

Biomarker sub-study

Patients from Quebec only (first or second line treatment)

No interventions assigned to this group

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role collaborator

Quebec Clinical Research Organization in Cancer

OTHER

Sponsor Role collaborator

PeriPharm

OTHER

Sponsor Role collaborator

Personalized Medicine Partnership for Cancer

OTHER

Sponsor Role collaborator

Jewish General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Dr. Jason Agulnik

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jason Agulnik, MD

Role: PRINCIPAL_INVESTIGATOR

Jewish General Hospital

Victor Cohen, MD

Role: PRINCIPAL_INVESTIGATOR

Jewish General Hospital

Locations

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Ottawa Hospital

Ottawa, Ontario, Canada

Site Status

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

McGill University Health Center (JGH, St-Mary's, MGH, RVH)

Montreal, Quebec, Canada

Site Status

Hôpital du Sacré-Coeur de Montréal

Montreal, Quebec, Canada

Site Status

Centre hospitalier de l'Université de Montréal

Montreal, Quebec, Canada

Site Status

CSSS Rimouski

Rimouski, Quebec, Canada

Site Status

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Site Status

Institut Universitaire de cardiologie et de pneumonologie

Québec, , Canada

Site Status

Countries

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Canada

References

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Katayama R, Shaw AT, Khan TM, Mino-Kenudson M, Solomon BJ, Halmos B, Jessop NA, Wain JC, Yeo AT, Benes C, Drew L, Saeh JC, Crosby K, Sequist LV, Iafrate AJ, Engelman JA. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers. Sci Transl Med. 2012 Feb 8;4(120):120ra17. doi: 10.1126/scitranslmed.3003316. Epub 2012 Jan 25.

Reference Type BACKGROUND
PMID: 22277784 (View on PubMed)

Camidge DR, Doebele RC. Treating ALK-positive lung cancer--early successes and future challenges. Nat Rev Clin Oncol. 2012 Apr 3;9(5):268-77. doi: 10.1038/nrclinonc.2012.43.

Reference Type BACKGROUND
PMID: 22473102 (View on PubMed)

Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Janne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010 Oct 28;363(18):1693-703. doi: 10.1056/NEJMoa1006448.

Reference Type BACKGROUND
PMID: 20979469 (View on PubMed)

Doebele RC, Pilling AB, Aisner DL, Kutateladze TG, Le AT, Weickhardt AJ, Kondo KL, Linderman DJ, Heasley LE, Franklin WA, Varella-Garcia M, Camidge DR. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res. 2012 Mar 1;18(5):1472-82. doi: 10.1158/1078-0432.CCR-11-2906. Epub 2012 Jan 10.

Reference Type BACKGROUND
PMID: 22235099 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32055239 (View on PubMed)

Other Identifiers

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Q-CROC-05

Identifier Type: -

Identifier Source: org_study_id

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