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

NCT02041468 | Unknown

• 1 other identifier: Q-CROC-05
• Study Type: observational
• Target: 29
• Locations: 1 country
• Sites: 8

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.

Conditions

Non-small Cell Lung Cancer Metastatic

Keywords

ALK-positive

Outcome Measures

Primary Outcomes (1)

• The pharmacoeconomic impact of using personalized medicine for the treatment of ALK+ lung cancer.

  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

  From the date of registration until date of death from any cause, assessed up to 60 months.

Secondary Outcomes (3)

• Type of resistance mechanisms identified in crizotinib-resistant tumors

  At progression of disease, an expected average of 24 months.

• 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.

• Number of participants with adverse events related to the biopsy procedure.

  Up to 4 years.

Study Arms (2)

Pharmacoeconomic main study

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

Biomarker sub-study

Patients from Quebec only (first or second line treatment)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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
• years of age or older

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jewish General Hospital: lead
• Pfizer: collaborator
• Quebec Clinical Research Organization in Cancer: collaborator
• PeriPharm: collaborator
• Personalized Medicine Partnership for Cancer: collaborator

Study Sites (8)

Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

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

Montreal, Quebec, H3T 1E2, Canada

Location

Hôpital du Sacré-Coeur de Montréal

Montreal, Quebec, H4J 1C5, Canada

Location

Centre hospitalier de l'Université de Montréal

Montreal, Quebec, Canada

Location

CSSS Rimouski

Rimouski, Quebec, G5L 5T1, Canada

Location

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Institut Universitaire de cardiologie et de pneumonologie

Québec, G1V 4G5, Canada

Location

Related Publications (5)

• 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.

  PMID: 22277784 BACKGROUND

• 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.

  PMID: 22473102 BACKGROUND

• 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.

  PMID: 20979469 BACKGROUND

• 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.

  PMID: 22235099 BACKGROUND

• 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.

  PMID: 32055239 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

The study will collect plasma, platelet-depleted plasma, tumor tissue (biopsy of a metastatic site that has acquired resistant to treatment) and primary archived tissue.

Study Officials

• Jason Agulnik, MD

  Jewish General Hospital

  PRINCIPAL INVESTIGATOR

• Victor Cohen, MD

  Jewish General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 20, 2013
• First Posted: January 22, 2014
• Study Start: January 1, 2014
• Primary Completion: March 1, 2018
• Study Completion: June 1, 2018
• Last Updated: August 30, 2017

Record last verified: 2017-08

Locations

CA (8)