Descriptive Observational Study ALK-2016-CPHG (ALK2016CPHG)

CHARACTERISTICS OF ADULT PATIENTS TREATED WITH CRIZOTINIB FOR ADVANCED NON-SMALL-CELL LUNG CANCER (NSCLC) WITH ALK GENE REARRANGEMENT OR ROS1 GENE REARRANGEMENT IN GENERAL HOSPITALS.

Descriptive Observational Study.

Characteristics Of ALK-positive and ROS1-positive Adults Patients Non-Small Cell Lung Cancer (NSCLC) Treated With Crizotinib Within General Hospitals

Study Overview

• Status: Completed
• Conditions: NSCLC; Crizotinib; ALK Gene Rearrangement or ROS1 Gene Rearrangement

Detailed Description

Describe the characteristics of patients treated with crizotinib Describe efficacy, safety, observance and QoL.

• Study Type: Observational
• Enrollment (Actual): 73

Contacts and Locations

Study Locations

• France
  • Aix en Provence, France, 13616
    • Centre Hospitalier Intercommunal du Pays d'Aix-Pertuis,Service de Pneumologie
  • Amiens, France, 80000
    • Clinique de L Europe
  • Aulnay sous Bois, France, 93 602
    • Hopital Robert Ballanger, Service de Pneumologie
  • Avignon, France, 84902
    • Centre Hospitalier d Avignon
  • Beauvais, France, 60021
    • Centre Hospitalier de Beauvais
  • Beziers, France, 34525
    • Centre Hospitalier General Beziers, Service De Pneumologie
  • Cannes, France, 06414
    • Centre Hospitalier de Cannes
  • Chalon sur Saone, France, 71321
    • Centre Hospitalier Chalon sur Saone William Morey
  • Chambery, France, 73000
    • Centre Hospitalier Metropole de Savoie-Site de Chambery
  • Colmar Cedex, France, 68024
    • Hopitaux Civils de Colmar - Hopital Louis Pasteur
  • Contamine sur Arve, France, 74130
    • Centre hospitalier Alpes Léman
  • Frejus, France, 83600
    • Centre Hospitalier Intercommunal Frejus
  • La Roche Sur Yon, France, 85925
    • CHD Vendee
  • La Roche Sur Yon Cedex 9, France, 85925
    • Centre Hospitalier Departemental Les Oudairies
  • Le Mans, France, 72037
    • Le Mans Hospital Center
  • Longjumeau, France, 91161
    • Centre Hospitalier des Deux Vallees - Longjumeau BP 125
  • Macon cedex, France, 71018
    • Centre Hospitalier de Mâcon
  • Marseille, France, 13003
    • Hopital Europeen - Service de Pneumologie
  • Mulhouse, France, 68051
    • GHR Mulhouse Sud Alsace
  • Nevers, France, 58033
    • Centre Hospitalier de l'Agglomeration de Nevers
  • Orleans, France, 45000
    • Centre Hospitalier Regional d Orleans
  • Pringy, France, 74374
    • Centre Hospitalier Annecy Genevois
  • Saint Pierre La Réunion, France, 97448
    • Groupe Hospitalier Sud Réunion
  • Thonon les Bains, France
    • Hopitaux du Leman
  • Troyes, France, 10003
    • Centre Hospitalier de Troyes, Service de Pneumologie - Oncologie Thoracique
  • Villefranche sur Saone, France, 69655
    • Centre Hospitalier de Villefranche sur Saone - BP80436

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants with ALK positive or ROS1-positive Locally advanced or metastatic non-small cell lung cancer NSCLC, initiated in the previous 3 months or participants initiating crizotinib treatment regardless of the line of treatment

Description

Inclusion criteria

• Age ≥ 18 years
• Locally advanced or metastatic NSCLC
• Patient ALK gene rearrangement or ROS1 gene rearrangement
• Patient having initiated in the previous 3 months or patient initiating crizotinib treatment regardless of the line of treatment
• Patient followed up by a physician in a hospital pulmonary medicine department
• Subject of reproductive age, using an effective method of contraception
• Patient informed verbally and in writing on the study and having consented to his/her personal data being collected within the scope of the study.

Non-inclusion criteria

• Patient included within the scope of an interventional therapeutic trial
• Patient not presenting with ALK gene rearrangement or ROS1 gene rearrangement
• Patient not available for follow-up throughout the duration of the study
• Patient deemed to be incapable of responding to the study questions for linguistic, cognitive or organisational reasons.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age: Line of Treatment		Baseline
Body Weight: Line of Treatment and Gene Rearrangement	Body weight in kilograms (kg) measured at baseline were reported.	Baseline
Body Mass Index (BMI): Line of Treatment and Gene Rearrangement	BMI was obtained by dividing body weight in kilograms (kg) by height in meters square (m^2).	Baseline
Gender: Line of Treatment		Baseline
Number of Participants Classified According to Smoking Status at Baseline: Line of Treatment and Gene Rearrangement	Number of participants were classified according to smoking status as non-smoker, ex-smoker (did not smoke in at least 1 year prior to baseline) and current-smoker.	Baseline
Number of Pack Years: Line of Treatment and Gene Rearrangement	The number of pack-years was calculated at baseline for ex-smokers and current smokers by multiplying the number of packs they consumed per day and the number of years that the participant had smoked this quantity of packs. Combined data is reported for ex-smokers and current smokers.	Baseline
Duration of Smoking and Duration of Quitting Smoke: Line of Treatment and Gene Rearrangement	Duration of smoking: a) for ex-smokers, duration of smoking (years) was calculated by subtracting start year with year of smoking stop, b) for current smokers, duration of smoking (years) was calculated by subtracting start year with year of Inclusion visit date. Combined data of duration of smoking is reported for ex-smokers and current smokers. Duration of quitting smoke (years) for ex-smokers was calculated by subtracting year of smoking stop with year of inclusion visit date.	Baseline
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Assessment: Line of Treatment and Gene Rearrangement	Number of participants were categorized as yes or no, according to have undergone assessment with ECOG performance status. ECOG performance status was used to measure quality of life of oncology participants with scores running from 0 (no severity) to 5 (maximum severity); where 0= fully active, able to carry on all pre-disease performance without restriction; 1= restricted in physically strenuous activity, ambulatory, able to carry out light or sedentary work; 2= ambulatory, capable of all self-care, unable to carry out any work activity, up greater than (>) 50 percent (%) of waking hours; 3= capable of only limited self-care, confined to bed or chair >50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed or chair; 5= dead.	Baseline
Number of Participants Categorized According to ECOG Performance Status Scores: Line of Treatment and Gene Rearrangement	ECOG performance status was used to measure quality of life of oncology patients with scores running from 0 (no severity) to 5 (maximum severity); where 0= fully active, able to carry on all pre-disease performance without restriction; 1= restricted in physically strenuous activity, ambulatory, able to carry out light or sedentary work; 2= ambulatory, capable of all self-care, unable to carry out any work activity, up >50% of waking hours; 3= capable of only limited self-care, confined to bed or chair >50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed or chair; 5= dead. Participants were categorized according to ECOG performance status scores of 0-1 and >=2.	Baseline
Time Since Diagnosis of NSCLC: Treatment and Gene Rearrangement	Time since diagnosis of NSCLC (months) was calculated as: inclusion visit date minus date of the biopsy that enabled making the diagnosis divided by 365.35/12. If the day of the diagnosis was missing, it was replaced by the 15th of the month for calculation.	Baseline
Number of Participants Categorized According to Type of Tumor's Histology: Line of Treatment and Gene Rearrangement	Participants were categorized according to type of tumor's histology as adenocarcinoma, carcinoma indifferencier and other.	Baseline
Number of Participants Categorized According to Tumor Stage: Line of Treatment and Gene Rearrangement	Participants were categorized according to tumor stage as IIIA/B or IVA/B classified as per Tumor Node Metastasis (TNM), 8th edition. TNM: based on tumor size, if cancer cells had spread to nearby lymph nodes (LN), or distant (other parts of body) metastasis. Stages included: stage 0 (no evidence of cancer cells), stage l (T1N0M0), stage IIA (T0N1M0, T1N1M0, T2N0M0), stage IIB (T2N1M0, T3N0M0), stage IIIA (T0N2M0, T1N2M0, T2N3M0, T3N1 or N2M0), stage IIIb (T4 any NM0, any TN3M0), stage IIIC (any TN3M0), stage IV (any T any NM1), where T0= early form of tumor, T1=<2 centimeter (cm), T2 =2-5 cm, T3=>2 cm, T4=large sized, N0= not spread to LN, N1= spread to 1 to 3, N2= spread to 4 to 9, N3= spread >10 axillary LN, M0= no metastasis, M1= metastasis. Tumor stage categories with at least 1 participant in any reporting arm are reported.	Baseline
Number of Participants Categorized According to Tumor Location: Line of Treatment and Gene Rearrangement	Participants were categorized according to location of tumor: upper right lobe, upper left lobe, middle right lobe, lower right lobe, and lower left lobe.	Baseline
Number of Participants Categorized According to Presence of Metastases: Line of Treatment and Gene Rearrangement	Participants were categorized according to presence of metastases as Yes or No.	Baseline
Number of Participants Categorized According to Number of Metastatic Sites: Line of Treatment and Gene Rearrangement	Participants were categorized according to number of metastatic sites.	Baseline
Number of Participants Categorized According to Location of Metastases: Line of Treatment and Gene Rearrangement	Participants were categorized according to the location of metastases. Participant could have more than 1 location of metastases.	Baseline
Time Since the First Strategy Start to Crizotinib Initiation: Line of Treatment and Gene Rearrangement	Time since the first strategy start to crizotinib initiation (months) was calculated as: crizotinib initiation date minus start date of the first strategy divided by 365.35/12. If the start date was missing, it was replaced by the 15th of the month for calculation.	Baseline
Number of Participants Categorized as "Yes" or "No" for Different Lines of Previous Chemotherapy: Line of Treatment and Gene Rearrangement	Number of participants were categorized according to the different lines of chemotherapy.	Baseline
Number of Cycles for Different Lines of Previous Chemotherapy: Line of Treatment and Gene Rearrangement	In this outcome measure, median of number of cycles for different lines of chemotherapy were reported.	Baseline
Duration of Different Lines of Previous Chemotherapy: Line of Treatment and Gene Rearrangement	In this outcome measure, median duration of different lines of chemotherapy was reported. Duration of chemotherapy (months) was calculated as = End date of the last cycle minus start date of the first cycle plus 1 divided by 365.25/12. If the day of the date was missing, it was replaced by the 15th of the month. If the month of the date was missing, the duration was considered as missing.	Baseline
Number of Participants Categorized as "Yes" or "No" for Previous Brain Irradiation Therapy, Previous Radiotherapies and Previous Tyrosine Kinase Inhibitor Therapy: Line of Treatment and Gene Rearrangement	In this outcome measure, participants were categorized according to the previous treatments received. Participant could have received more than 1 type of previous therapies.	Baseline
Dose of Previous Brain Irradiation and Radiotherapies: Line of Treatment and Gene Rearrangement	In this outcome measure, median of dose of brain irradiation and radiotherapies were reported.	Baseline
Duration of Previous Brain Irradiation Therapy and Radiotherapies: Line of Treatment and Gene Rearrangement	In this outcome measure, duration of previous brain irradiation therapy and radiotherapies was reported.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Categorized According to Diagnostic Method to Detect ALK and ROS1 Gene Rearrangement: Line of Treatment and Gene Rearrangement	In this outcome measure, the number of participants were categorized according to diagnostic method used to detect ALK and ROS1 gene rearrangement.	Baseline
Number of Participants Categorized According to Origin of Specimen to Detect ALK and ROS1 Gene Rearrangement: Line of Treatment and Gene Rearrangement	In this outcome measure, number of participants were categorized according to origin of specimen to detect ALK and ROS1 gene rearrangement. Origins of specimen included: primitive tumor, thoracic lymph node, extrathoracic lymph node, bone, adrenal glands and pleural.	Baseline
Number of Participants Categorized According to Analysis Platform to Detect ALK and ROS1 Gene Rearrangement: Line of Treatment and Gene Rearrangement	In this outcome measure, number of participants were categorized according to analysis platform to detect ALK and ROS1 gene rearrangement. Analysis platform included following sites: University hospital center (UHC) Alsace Cancer center of Strasbourg - Hospital Center of Mulhouse - Hospital Center of Colmar; UHC Aquitaine - Hospital Center de Bordeaux - La Réunion; UHC Bourgogne - Hospital Center of Dijon, UHC of Tours - Orléans; UHC Haute-Normandie - Hospital Center of Rouen, Ile-de-France AP - HP; UHC Languedoc Roussillon - Hospital Center of Montpellier - UHC of Nîmes; UHC Nord-Pas-de-Calais - Hospital Center of Lille; UHC Pays-de-la-Loire - Hospital Center of Nantes; UHC Pays-de-la-Loire - Hospital Center of Angers; UHC Picardie, Amiens; UHC Provence Alpes Côte d'Azur - Hospital Center of Nice; UHC Provence Alpes Côte d'Azur - Hospital Center of Marseille; UHC Rhône Alpes - Hospital Center of Lyon; UHC Rhône Alpes - Hospital Center of Grenoble; and other platform.	Baseline
Number of Participants Categorized According to Technique Used to Detect ALK and ROS1 Gene Rearrangement: Line of Treatment and Gene Rearrangement	In this outcome measure, number of participants were categorized according to the techniques used to detect ALK and ROS1 gene rearrangement. Techniques involved were: Immunohistochemistry (IHC); Fluorescence in situ hybridisation (FISH); Reverse transcriptase polymerase chain reaction (RT-PCR); Next-Generation Sequencing (NGS); Other; and Associations-FISH, IHC, IHC+FISH, IHC+FISH+NGS, NGS.	Baseline
Duration Between Sending and Receipt of ALK and ROS1 Results: Line of Treatment and Gene Rearrangement	Duration between sending and receipt of ALK for positive ALK was calculated in days by subtracting the date sent to the platform from date when positive ALK result was received. Duration between sending and receipt of ROS1 for positive ROS1 was calculated in days by subtracting the date sent to the platform from date when positive ROS1 result was received.	Baseline
Number of Participants Among Whom Search for Other Biological Markers Was Carried Out: Line of Treatment and Gene Rearrangement	In this outcome measure, number of participants were categorized "Yes" or "No" for search of other biological markers.	Baseline
Number of Participants Categorized According to Clinical Response at Month 3, 6, 9, 12, 15 and 18	Number of participants were categorized according to clinical response as evaluated by physician. Clinical response was categorized into disease improvement, disease stabilization or disease degradation.	Month 3, 6, 9, 12, 15 and 18
Number of Participants Categorized According to Tumor Response at Month 3, 6, 9, 12, 15 and 18	Number of participants were categorized according to tumor response per Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. Tumor response included total (complete) response (CR), partial response (PR), stable disease (SD) or disease progression (PD) on imaging. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Persistence of one or more non-target lesion and/or maintenance of tumor marker level above the normal limits. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. Unequivocal progression of existing non-target lesions. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	Month 3, 6, 9, 12, 15 and 18
Time Since Diagnosis to Progression at Month 3, 6, 9, 12, 15 and 18	Time since diagnosis to progression (months) was calculated as: progression date minus date of biopsy that enabled making the diagnosis divided by 365.35/12. If the day of the diagnosis was missing, it was replaced by the 15th of the month for calculation. If the day of the progression was missing, it was replaced by the 1st of the month for calculation.	Month 3, 6, 9, 12, 15 and 18
Number of Participants With Site of Progression as Primary Tumor at Month 3, 6, 9, 12, 15 and 18	In this outcome measure, number of participants whose progression was noted at primary tumor site were reported.	Month 3, 6, 9, 12, 15 and 18
Number of Participants With Site of Progression as Already Existing Metastasis at Month 3, 6, 9, 12, 15 and 18	In this outcome measure, number of participants whose progression was noted at already existing metastasis sites were reported.	Month 3, 6, 9, 12, 15 and 18
Number of Participants Categorized According to Location of Progression in Already Existing Metastasis at Month 3, 6, 9, 12, 15 and 18	In this outcome measure, participants were categorized according to location of progression in already existing metastasis which were located at adrenal glands, bone, brain, liver, lymph node, pleural, plueral liver, pleural lymph node, brain pleural, and kidney. Only those rows are reported with at least 1 participant as data for any reporting arm.	Month 3, 6, 9, 12, 15 and 18
Number of Participants With Site of Progression as New Metastases at Month 3, 6, 9, 12, 15 and 18	In this outcome measure, participants with new metastases as the site of progression were reported.	Month 3, 6, 9, 12, 15 and 18
Number of Participants Categorized According to Location of Site of Progression as New Metastases at Month 3, 6, 9, 12, 15 and 18	In this outcome measure, number of participants were categorized according to progression at location of new metastases. Location of new metastases included contralateral lung, extrathoracic lymph node, brain, liver, bone, adrenal glands, lymphangite carcinomateuse and pleural. Only those categories in which at least 1 participant had data were reported.	Month 3, 6, 9, 12, 15 and 18
Treatment Duration Until Progression With Brain Metastases	Treatment duration until progression with brain metastases (weeks) was calculated as: ([date of progression - first treatment intake date] + 1) divided by 7. If the day of the progression was missing, it was replaced by the 1st of the month for calculation.	Baseline
Number of Participants With Biopsy on Progression at Month 3, 6, 9, 12, 15 and 18	In this outcome measure, number of participants were categorized on the basis of conduction of biopsy on progression as "Yes' or "No".	Month 3, 6, 9, 12, 15 and 18
Objective Response Rate (ORR)	The objective response rate was defined as the percentage of participants with complete response (CR) or partial response (PR) based on RECIST v1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Persistence of one or more non-target lesion and/or maintenance of tumor marker level above the normal limits.	Maximum up to 18 months
Disease Control Rate (DCR) at Month 12 and 18	DCR at 12 and 18 months was defined as the percentage of participants with CR, PR or SD at 12 and at 18 months. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Persistence of one or more non-target lesion and/or maintenance of tumor marker level above the normal limits. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study or unequivocal progression of existing non-target lesions), taking as reference the smallest sum diameters while on study.	Month 12, 18
European Organization for Research and Treatment of Cancer (EORTC) Lung Cancer (LC) Module 13 Symptom Scales Scores at Baseline, Month 3, 6, 9, 12, 15 and 18	EORTC QLQ-LC13 consisted of following symptom scales/items: coughing, haemoptysis, dyspnoea, dyspnoea when resting, dyspnoea when walking, dyspnoea when stairs, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts and pain relief after medication. The dyspnoea scale was only calculated if all three items had been answered. Some respondents ignore question "dyspnoea when stairs" because they never climbed stairs. Hence if item "dyspnoea when stairs" was missing then items "dyspnoea when resting" and "dyspnoea when walking" was used as single-item measures under item "dyspnoea". Transformed scores for each item ranged from 0 to 100, higher score is indicative of a higher response level (a high score for a symptom scale/item represents a high level of symptomatology/problems).	Baseline, Month 3, 6, 9, 12, 15, 18
Time to Median Progression Free Survival (Months) With Its 95%CI	PFS was defined as the time between the treatment start (date of the first Crizotinib intake) and the date of the first disease progression or the all-cause death. Participants who did not progress or were still alive at the end of the study or at the date of cut-off were censored at the last disease evaluation date.	18 months
18-Month Overall Survival (OS) Rate (95%CI)	OS was defined as the time from the date of first dose of study drug to the date of death due to any cause. Participants last known to be alive were censored at the date of last contact. 18-month OS rates was assessed by Kaplan-Meier method with right censoring.	18 months
Number of Participants Per Morisky Score Classification at Month 3, 6, 9, 12, 15 and 18	Compliance to study drug was evaluated using Morisky score. The questionnaire consisted of 4 questions in which the scale was 0 for "yes" (indicating poor compliance) and 1 for "no" (indicating good compliance). The items were summed to give a range of scores from 0 to 4. A score of 4 indicated high compliance, 2-3 indicated medium compliance and 0-1 indicated low compliance.	Month 3, 6, 9, 12, 15 and 18
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Serious AE: any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and all Non-SAEs.	Up to maximum of 18 months

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: French College of General Hospital Pneumologists (CPHG)
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2017
• Primary Completion (Actual): July 1, 2020
• Study Completion (Actual): July 1, 2020

Study Registration Dates

• First Submitted: March 5, 2018
• First Submitted That Met QC Criteria: October 22, 2018
• First Posted (Actual): October 24, 2018

Study Record Updates

• Last Update Posted (Actual): September 27, 2024
• Last Update Submitted That Met QC Criteria: June 4, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Non-Small Cell Lung Cancer (NSCLC); crizotinib; ALK gene rearrangement or ROS1 gene rearrangement
• Other Study ID Numbers: A8081060; ALK-2016-CPHG (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No