Non-small Cell Lung Cancer MetastaticNCT02041468
Study to Evaluate Resistance Mechanisms and Real-world Pharmacoeconomics of Crizotinib in NSCLC Patients
An observational study of Non-small Cell Lung Cancer Metastatic, run by Jewish General Hospital at 8 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer Metastatic
- How many people
- 29 participants
- Where
- 8 sitesCanada
- Study dates
- Jan 2014to Jun 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) found positive for ALK mutation from participating hospitals in Quebec.
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Canada8 sites
McGill University Health Center (JGH, St-Mary's, MGH, RVH)
Montreal, Quebec, H3T 1E2
Hôpital du Sacré-Coeur de Montréal
Montreal, Quebec, H4J 1C5
Centre hospitalier de l'Université de Montréal
Montreal, Quebec
Ottawa Hospital
Ottawa, Ontario, K1H 8L6
Institut Universitaire de cardiologie et de pneumonologie
Québec, G1V 4G5
CSSS Rimouski
Rimouski, Quebec, G5L 5T1
Centre Hospitalier Universitaire de Sherbrooke
Sherbrooke, Quebec, J1H 5N4
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
About this study
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
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:
Read more
- 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.
Read the 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.
- Conditions
- Non-small Cell Lung Cancer Metastatic
- Keywords
- ALK-positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
A biopsy will be taken from a metastatic lesion that has progressed despite treatment with crizotinib. Genomic material will be isolated and sequenced to identify causes of acquired resistance to crizotinib.
Measured: At progression of disease, an expected average of 24 months.
Change in blood-based biomarkers of response to crizotinib.
Plasma will be isolated from patients pre-treatment, at every disease assessment, at progression of disease, and at treatment discontinuation. This will be used to identify changes in blood-based biomarkers using proteomics analysis by mass spectrometry.
Measured: 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.
Adverse events possibly, probably or definitely related to the biopsy procedure will be reported according to the The NCI's Common Toxicity Criteria version 4.0
Measured: Up to 4 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2014 (estimated)
- Study startJan 2014
- Primary completionMar 2018 (estimated)
- Study completionJun 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Non-small Cell Lung Cancer MetastaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jewish General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, Quebec Clinical Research Organization in Cancer, PeriPharm, Personalized Medicine Partnership for Cancer
- Responsible party
- Principal investigator, Dr. Jason Agulnik, Jewish General Hospital
- Investigators
- Jason Agulnik, MD, Principal investigator, Jewish General HospitalVictor Cohen, MD, Principal investigator, Jewish General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02041468
- Sponsor's protocol ID
- Q-CROC-05
- Status last verified
- Aug 2017
- First submitted
- 20 Dec 2013
- Last updated
- 30 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 22277784Camidge 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.
PubMed 22473102Kwak 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.
PubMed 20979469Doebele 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.
PubMed 22235099Couetoux 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.
PubMed 32055239
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02041468
- Acronym / sponsor ID
- Q-CROC-05
- Conditions
- Non-small Cell Lung Cancer Metastatic
- Keywords
- ALK-positive
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Jewish General HospitalUniversity, hospital or other
- Collaborators
- Pfizer, Quebec Clinical Research Organization in Cancer, PeriPharm, Personalized Medicine Partnership for Cancer
- Study start
- Jan 2014
- Primary completion
- Mar 2018 (estimated)
- Study completion
- Jun 2018 (estimated)
- First posted
- 22 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) found positive for ALK mutation from participating hospitals in Quebec.
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The pharmacoeconomic impact of using personalized medicine for the treatment of ALK+ lung cancer.
Time frame: 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
3 secondary outcomes
Type of resistance mechanisms identified in crizotinib-resistant tumors
Time frame: At progression of disease, an expected average of 24 months.
Change in blood-based biomarkers of response to crizotinib.
Time frame: 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.
Time frame: Up to 4 years.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2017.
- Background: PubMed 22277784Katayama 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.
- Background: PubMed 22473102Camidge 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.
- Background: PubMed 20979469Kwak 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.
- Background: PubMed 22235099Doebele 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.
- Derived from this study: PubMed 32055239Couetoux 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason Agulnik, MD principal investigator
Jewish General Hospital
Victor Cohen, MD principal investigator
Jewish General Hospital
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Non-small Cell Lung Cancer Metastatic, run by Jewish General Hospital at 8 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The pharmacoeconomic impact of using personalized medicine for the treatment of ALK+ lung cancer. (time frame: From the date of registration until date of death from any cause, assessed up to 60 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02041468, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2017.