Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03052608




Registration number
NCT03052608
Ethics application status
Date submitted
20/01/2017
Date registered
14/02/2017
Date last updated
26/06/2024

Titles & IDs
Public title
A Study Of Lorlatinib Versus Crizotinib In First Line Treatment Of Patients With ALK-Positive NSCLC
Scientific title
A PHASE 3, RANDOMIZED, OPEN-LABEL STUDY OF LORLATINIB (PF-06463922) MONOTHERAPY VERSUS CRIZOTINIB MONOTHERAPY IN THE FIRST-LINE TREATMENT OF PATIENTS WITH ADVANCED ALK-POSITIVE NON-SMALL CELL LUNG CANCER
Secondary ID [1] 0 0
2016-003315-35
Secondary ID [2] 0 0
B7461006
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Non-Small-Cell Lung 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Lorlatinib
Treatment: Drugs - Crizotinib

Experimental: Lorlatinib - Lorlatinib single agent, 100 mg (4 x 25 mg) oral tables, QD, continuously

Active comparator: Crizotinib - Crizotinib single agent, 250 mg (1 x 250) oral capsules, BID, continuously


Treatment: Drugs: Lorlatinib
ALK-positive NSCL treatment

Treatment: Drugs: Crizotinib
ALK-positive NSCL treatment
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) Assessment
Timepoint [1] 0 0
From time of Study Start up to 33 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From time of Study Start up to 33 months
Secondary outcome [2] 0 0
Progression-Free Survival (PFS) Based on Investigator's Assessment
Timepoint [2] 0 0
From time of Study Start up to 33 months
Secondary outcome [3] 0 0
Objective Response Rate (ORR) - Percentage of Participants With Objective Response (OR) Based on BICR Assessment
Timepoint [3] 0 0
From time of Study Start up to 33 months
Secondary outcome [4] 0 0
Objective Response Rate (ORR) - Percentage of Participants With Objective Response (OR) Based on Investigator's Assessment
Timepoint [4] 0 0
From time of Study Start up to 33 months
Secondary outcome [5] 0 0
Intracranial Objective Response Rate (IC-ORR) - Percentage of Participants With Intracranial Objective Response (IC-OR) Based on BICR Assessment
Timepoint [5] 0 0
From time of Study Start up to 33 months
Secondary outcome [6] 0 0
Intracranial Time to Progression (IC-TTP) Based on BICR Assessment
Timepoint [6] 0 0
From time of Study Start up to 33 months
Secondary outcome [7] 0 0
Duration of Response (DR) Based on BICR Assessment
Timepoint [7] 0 0
From time of Study Start up to 33 months
Secondary outcome [8] 0 0
Intracranial Duration of Response (IC-DR) Based on BICR Assessment
Timepoint [8] 0 0
From time of Study Start up to 33 months
Secondary outcome [9] 0 0
Time to Tumor Response (TTR) Based on BICR Assessment
Timepoint [9] 0 0
From time of Study Start up to 33 months
Secondary outcome [10] 0 0
Intracranial Time to Tumor Response (IC-TTR) Based on BICR Assessment
Timepoint [10] 0 0
From time of Study Start up to 33 months
Secondary outcome [11] 0 0
PFS2 Based on Investigator's Assessment
Timepoint [11] 0 0
From time of Study Start up to 45 months
Secondary outcome [12] 0 0
Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related)
Timepoint [12] 0 0
From time of Study Start up to 33 months
Secondary outcome [13] 0 0
Number of Participants With Changes in Hematology Laboratory Parameters From Baseline Maximum NCI-CTCAE Grade Lower Than 3 to Postbaseline Maximum Grade 3 or Grade 4
Timepoint [13] 0 0
From Baseline up to 33 months
Secondary outcome [14] 0 0
Number of Participants With Changes in Chemistry Laboratory Parameters From Baseline Maximum NCI-CTCAE Grade Lower Than 3 to Postbaseline Maximum Grade 3 or Grade 4
Timepoint [14] 0 0
From Baseline up to 33 months
Secondary outcome [15] 0 0
Number of Participants With Changes in Lipid Laboratory Parameters From Baseline Maximum NCI-CTCAE Grade Lower Than 3 to Postbaseline Maximum Grade 3 or Grade 4
Timepoint [15] 0 0
From Baseline up to 33 months
Secondary outcome [16] 0 0
Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria
Timepoint [16] 0 0
From Baseline up to 33 months
Secondary outcome [17] 0 0
Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria
Timepoint [17] 0 0
From Baseline up to 33 months
Secondary outcome [18] 0 0
Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Points in Left Ventricular Ejection Fraction (LVEF) Percentage
Timepoint [18] 0 0
From Baseline up to 33 months
Secondary outcome [19] 0 0
Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time
Timepoint [19] 0 0
Baseline, Cycle 2 Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C8D1, C10D1, C12D1, C14D1, C16D1, C18D1, C20D1, C22D1, C24D1, C26D1, C28D1, C30D1, C32D1, C34D1, C36D1, C38D1 and End of Treatment
Secondary outcome [20] 0 0
Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time
Timepoint [20] 0 0
Baseline, Cycle 2 Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C8D1, C10D1, C12D1, C14D1, C16D1, C18D1, C20D1, C22D1, C24D1, C26D1, C28D1, C30D1, C32D1, C34D1, C36D1, C38D1 and End of Treatment
Secondary outcome [21] 0 0
Change From Baseline in Global Quality of Life (QOL), Functional Scales and Symptoms Scales as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) During Overall Treatment
Timepoint [21] 0 0
From Baseline up to Cycle 38 Day 1
Secondary outcome [22] 0 0
Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment
Timepoint [22] 0 0
From Baseline up to Cycle 38 Day 1
Secondary outcome [23] 0 0
Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time
Timepoint [23] 0 0
Baseline, Day 1 of all cycles from Cycle 2 to Cycle 38, and End of Treatment
Secondary outcome [24] 0 0
Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time
Timepoint [24] 0 0
Baseline, Day 1 of all cycles from Cycle 2 to Cycle 38, and End of Treatment
Secondary outcome [25] 0 0
Time to Deterioration (TTD) in Participant Reported Pain in Chest, Dyspnea, or Cough From QLQ-LC13
Timepoint [25] 0 0
From Baseline up to 33 months
Secondary outcome [26] 0 0
Number of Participant With ALK Domain Mutation in Plasma Circulating Nucleic Acid (CNA) Analysis at Screening, Cycle 2 Day 1 and Cycle 7 Day 1
Timepoint [26] 0 0
at Screening, Cycle 2 Day 1 and Cycle 7 Day 1
Secondary outcome [27] 0 0
Number of Participant With ALK Fusion Variant in Plasma Circulating Nucleic Acid (CNA) Analysis at Screening, Cycle 2 Day 1 and Cycle 7 Day 1
Timepoint [27] 0 0
at Screening, Cycle 2 Day 1 and Cycle 7 Day 1

Eligibility
Key inclusion criteria
* Histologically or cytologically confirmed diagnosis of locally advanced or metastatic ALK-positive NSCLC; at least 1 extracranial measurable target lesion not previously irradiated. CNS metastases allowed if asymptomatic and not currently requiring corticosteroid treatment.
* Availability of an archival FFPE tissue specimen.
* No prior systemic NSCLC treatment.
* ECOG PS 0, 1, or 2.
* Age =18 years .
* Adequate Bone Marrow, Liver, Renal, Pancreatic Function
* Negative pregnancy test for females of childbearing potential
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Spinal cord compression unless good pain control attained
* Major surgery within 4 weeks prior to randomization.
* Radiation therapy within 2 weeks prior to randomization, including stereotactic or partial brain irradiation. Whole brain irradiation within 4 weeks prior to randomization
* Active bacterial, fungal, or viral infection
* Clinically significant cardiovascular disease, active or within 3 months prior to enrollment. Ongoing cardiac dysrhythmias, uncontrolled atrial fibrillation, bradycardia or congenital long QT syndrome
* Predisposing characteristics for acute pancreatitis in the last month prior to randomization.
* History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease
* Active malignancy (other than NSCLC, non melanoma skin cancer, in situ cervical cancer, papillary thyroid cancer, LCIS/DCIS of the breast, or localized prostate cancer) within the last 3 years prior to randomization.
* Concurrent use of any of the following food or drugs within 12 days prior to the first dose of lorlatinib or crizotinib.

1. known strong CYP3A inhibitors .
2. known strong CYP3A inducers
3. known P gp substrates with a narrow therapeutic index
* Concurrent use of CYP3A substrates with narrow therapeutic indices within 12 days prior to the first dose of lorlatinib or crizotinib.
* Other severe acute or chronic medical or psychiatric condition, including recent or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or interfere with the interpretation of study results
* Investigational site staff members directly involved in the conduct of the study and their family members, or Pfizer employees, including their family members, directly involved in the conduct of the study.
* Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry and/or during study participation.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/04/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2028
Actual
Sample size
Target
Accrual to date
Final
296
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Bendigo Day Surgery Collection Centre and Laboratory - Bendigo
Recruitment hospital [2] 0 0
Bendigo Medical Imaging, Bendigo Hospital - Bendigo
Recruitment hospital [3] 0 0
Melbourne Pathology - Bendigo
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3550 - Bendigo
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
United States of America
State/province [5] 0 0
Washington
Country [6] 0 0
Argentina
State/province [6] 0 0
Buenos Aires
Country [7] 0 0
Argentina
State/province [7] 0 0
Caba
Country [8] 0 0
Belgium
State/province [8] 0 0
Charleroi
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Canada
State/province [10] 0 0
Quebec
Country [11] 0 0
China
State/province [11] 0 0
Beijing
Country [12] 0 0
China
State/province [12] 0 0
Jilin
Country [13] 0 0
China
State/province [13] 0 0
Shanghai
Country [14] 0 0
China
State/province [14] 0 0
Zhejiang
Country [15] 0 0
China
State/province [15] 0 0
Guangzhou
Country [16] 0 0
Czechia
State/province [16] 0 0
Olomouc
Country [17] 0 0
Czechia
State/province [17] 0 0
Praha 2
Country [18] 0 0
France
State/province [18] 0 0
Aquitaine
Country [19] 0 0
France
State/province [19] 0 0
Chevilly Larue
Country [20] 0 0
France
State/province [20] 0 0
Le Mans
Country [21] 0 0
France
State/province [21] 0 0
Marseille cedex 09
Country [22] 0 0
France
State/province [22] 0 0
Marseille cedex 20
Country [23] 0 0
France
State/province [23] 0 0
Paris
Country [24] 0 0
France
State/province [24] 0 0
Rennes cedex 9
Country [25] 0 0
France
State/province [25] 0 0
Suresnes
Country [26] 0 0
France
State/province [26] 0 0
Toulouse Cedex 9
Country [27] 0 0
France
State/province [27] 0 0
Toulouse cedex 9
Country [28] 0 0
France
State/province [28] 0 0
Villejuif
Country [29] 0 0
Germany
State/province [29] 0 0
Dresden
Country [30] 0 0
Germany
State/province [30] 0 0
Heidelberg
Country [31] 0 0
Germany
State/province [31] 0 0
Homburg - Saar
Country [32] 0 0
Germany
State/province [32] 0 0
Regensburg
Country [33] 0 0
Hong Kong
State/province [33] 0 0
Hong Kong
Country [34] 0 0
India
State/province [34] 0 0
Haryana
Country [35] 0 0
India
State/province [35] 0 0
Karnataka
Country [36] 0 0
India
State/province [36] 0 0
Maharashtra
Country [37] 0 0
Italy
State/province [37] 0 0
CT
Country [38] 0 0
Italy
State/province [38] 0 0
MB
Country [39] 0 0
Italy
State/province [39] 0 0
MI
Country [40] 0 0
Italy
State/province [40] 0 0
PG
Country [41] 0 0
Italy
State/province [41] 0 0
PN
Country [42] 0 0
Italy
State/province [42] 0 0
PR
Country [43] 0 0
Italy
State/province [43] 0 0
RM
Country [44] 0 0
Italy
State/province [44] 0 0
Napoli
Country [45] 0 0
Italy
State/province [45] 0 0
Ravenna
Country [46] 0 0
Japan
State/province [46] 0 0
Aichi
Country [47] 0 0
Japan
State/province [47] 0 0
Ehime
Country [48] 0 0
Japan
State/province [48] 0 0
Fukuoka
Country [49] 0 0
Japan
State/province [49] 0 0
Hokkaido
Country [50] 0 0
Japan
State/province [50] 0 0
Ishikawa
Country [51] 0 0
Japan
State/province [51] 0 0
Kanagawa
Country [52] 0 0
Japan
State/province [52] 0 0
Miyagi
Country [53] 0 0
Japan
State/province [53] 0 0
Osaka
Country [54] 0 0
Japan
State/province [54] 0 0
Shizuoka
Country [55] 0 0
Japan
State/province [55] 0 0
Tokyo
Country [56] 0 0
Japan
State/province [56] 0 0
Yamaguchi
Country [57] 0 0
Japan
State/province [57] 0 0
Koto-ku, Tokyo
Country [58] 0 0
Japan
State/province [58] 0 0
Niigata
Country [59] 0 0
Japan
State/province [59] 0 0
Okayama
Country [60] 0 0
Japan
State/province [60] 0 0
Tokushima
Country [61] 0 0
Japan
State/province [61] 0 0
Wakayama
Country [62] 0 0
Korea, Republic of
State/province [62] 0 0
Gyeonggi-do
Country [63] 0 0
Korea, Republic of
State/province [63] 0 0
Seoul
Country [64] 0 0
Korea, Republic of
State/province [64] 0 0
Ulsan
Country [65] 0 0
Mexico
State/province [65] 0 0
Aguascalientes
Country [66] 0 0
Mexico
State/province [66] 0 0
Distrito Federal
Country [67] 0 0
Netherlands
State/province [67] 0 0
Groningen
Country [68] 0 0
Poland
State/province [68] 0 0
Gdansk
Country [69] 0 0
Poland
State/province [69] 0 0
Poznan
Country [70] 0 0
Poland
State/province [70] 0 0
Szczecin
Country [71] 0 0
Poland
State/province [71] 0 0
Warszawa
Country [72] 0 0
Russian Federation
State/province [72] 0 0
Kursk Region
Country [73] 0 0
Russian Federation
State/province [73] 0 0
OMSK Region
Country [74] 0 0
Russian Federation
State/province [74] 0 0
Saint-petersburg
Country [75] 0 0
Russian Federation
State/province [75] 0 0
Kursk
Country [76] 0 0
Russian Federation
State/province [76] 0 0
Moscow
Country [77] 0 0
Singapore
State/province [77] 0 0
Singapore
Country [78] 0 0
Spain
State/province [78] 0 0
Barcelona
Country [79] 0 0
Spain
State/province [79] 0 0
Canarias
Country [80] 0 0
Spain
State/province [80] 0 0
Madrid
Country [81] 0 0
Spain
State/province [81] 0 0
Navarra
Country [82] 0 0
Spain
State/province [82] 0 0
A Coruna
Country [83] 0 0
Spain
State/province [83] 0 0
Girona
Country [84] 0 0
Spain
State/province [84] 0 0
Valencia
Country [85] 0 0
Taiwan
State/province [85] 0 0
Taiwan ROC
Country [86] 0 0
Taiwan
State/province [86] 0 0
Kaohsiung
Country [87] 0 0
Taiwan
State/province [87] 0 0
Taichung
Country [88] 0 0
Taiwan
State/province [88] 0 0
Taipei
Country [89] 0 0
Turkey
State/province [89] 0 0
Adana
Country [90] 0 0
Turkey
State/province [90] 0 0
Istanbul
Country [91] 0 0
Turkey
State/province [91] 0 0
Izmir
Country [92] 0 0
United Kingdom
State/province [92] 0 0
Suffolk
Country [93] 0 0
United Kingdom
State/province [93] 0 0
WEST Midlands
Country [94] 0 0
United Kingdom
State/province [94] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
A phase 3 study to demonstrate whether lorlatinib given as monotherapy is superior to crizotinib alone in prolonging the progression-free survival in advanced ALK-positive NSCLC patients who are treatment naïve and to compare lorlatinib to crizotinib with respect to overall survival in the same population
Trial website
https://clinicaltrials.gov/study/NCT03052608
Trial related presentations / publications
Solomon BJ, Bauer TM, Ignatius Ou SH, Liu G, Hayashi H, Bearz A, Penkov K, Wu YL, Arrieta O, Jassem J, Calella AM, Peltz G, Polli A, Thurm H, Mok T. Post Hoc Analysis of Lorlatinib Intracranial Efficacy and Safety in Patients With ALK-Positive Advanced Non-Small-Cell Lung Cancer From the Phase III CROWN Study. J Clin Oncol. 2022 Nov 1;40(31):3593-3602. doi: 10.1200/JCO.21.02278. Epub 2022 May 23.
Solomon BJ, Bauer TM, de Marinis F, Felip E, Goto Y, Liu G, Mazieres J, Kim DW, Mok T, Polli A, Thurm H, Calella AM, Peltz G, Shaw AT. Plain language summary of the CROWN study comparing lorlatinib with crizotinib for people with untreated non-small cell lung cancer. Future Oncol. 2021 Dec 1;17(34):4649-4656. doi: 10.2217/fon-2021-0904. Epub 2021 Sep 29.
Shaw AT, Bauer TM, de Marinis F, Felip E, Goto Y, Liu G, Mazieres J, Kim DW, Mok T, Polli A, Thurm H, Calella AM, Peltz G, Solomon BJ; CROWN Trial Investigators. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2020 Nov 19;383(21):2018-2029. doi: 10.1056/NEJMoa2027187.
Shaw AT, Felip E, Bauer TM, Besse B, Navarro A, Postel-Vinay S, Gainor JF, Johnson M, Dietrich J, James LP, Clancy JS, Chen J, Martini JF, Abbattista A, Solomon BJ. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017 Dec;18(12):1590-1599. doi: 10.1016/S1470-2045(17)30680-0. Epub 2017 Oct 23.
Gainor JF, Shaw AT. J-ALEX: alectinib versus crizotinib in ALK-positive lung cancer. Lancet. 2017 Jul 1;390(10089):3-4. doi: 10.1016/S0140-6736(17)31074-7. Epub 2017 May 10. No abstract available.
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03052608