NCT01154140 · CITED IN SOURCE DOCUMENTS

A Clinical Trial Testing The Efficacy Of Crizotinib Versus Standard Chemotherapy Pemetrexed Plus Cisplatin Or Carboplatin In Patients With ALK Positive Non Squamous Cancer Of The Lung

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2017-11-06

This study will evaluate the anti-cancer effects of crizotinib when compared with standard chemotherapy in patients with ALK positive lung cancer.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression-Free Survival (PFS) Based on IRR

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Overall Survival Probability at Month 12 and 18

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outcome · POSTED

Objective Response Rate (ORR): Percentage of Participants With Objective Response as Assessed by IRR

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outcome · POSTED

Duration of Response (DR) Based on IRR

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outcome · POSTED

Time to Tumor Response (TTR) Based on IRR

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outcome · POSTED

Percentage of Participants With Disease Control at Week 12 Based on IRR

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outcome · POSTED

Time to Progression (TTP) Based on IRR

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outcome · POSTED

Time to Intracranial Progression (IC-TTP) Based on IRR

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outcome · POSTED

Time to Extracranial Progression (EC-TTP) Based on IRR

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outcome · POSTED

Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

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outcome · POSTED

Percentage of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)

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outcome · POSTED

Percentage of Participants With Adverse Events (AEs) According to Maximum Severity

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outcome · POSTED

Plasma Predose Concentration (Ctrough) of Crizotinib and Its Metabolite PF-06260182

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outcome · POSTED

Percentage of Participants For Each Anaplastic Lymphoma Kinase (ALK) Gene Fusion Variants

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outcome · POSTED

Objective Response Rate (ORR) of Anaplastic Lymphoma Kinase (ALK) Variant Groups Based on IRR

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outcome · POSTED

Time to Deterioration (TTD) in Chest Pain, Dyspnea or Cough

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outcome · POSTED

Change From Baseline in Functioning and Global Quality of Life (QOL) as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)

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outcome · POSTED

Change From Baseline Scores in QLQ-C30 Symptoms as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)

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outcome · POSTED

Change From Baseline in Lung Cancer Symptom Scores as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13)

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outcome · POSTED

Change From Baseline in General Health Status as Assessed by EuroQol 5D (EQ-5D)- Visual Analog Scale (VAS)

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outcome · POSTED

Percentage of Participants With Hospital Admissions-Healthcare Resource Utilization (HCRU)

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outcome · POSTED

Percentage of Participants With Laboratory Test Abnormalities By Maximum Severity: National Cancer Institute Common Terminology Criteria for Adverse Event (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities

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outcome · POSTED

Percentage of Participants With Laboratory Test Abnormalities By Maximum Severity: National Cancer Institute Common Terminology Criteria for Adverse Event (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Proven diagnosis of locally advanced not suitable for local treatment, recurrent and metastatic non-squamous cell carcinoma of the lung * Positive for translocation or inversion events involving the ALK gene locus * No prior systemic treatment for locally advanced or metastatic disease; Patients with brain metastases only if treated and neurologically stable with no ongoing requirement for corticosteroids * Evidence of a personally signed and dated informed consent document and willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures including completion of patient reported outcome \[PRO\] measures. * 18 years of age or older with the exception of India which has an upper age limit of 65 years old Exclusion Criteria: * Current treatment on another therapeutic clinical trial. * Prior therapy directly targeting ALK. * Any of the following within the 3 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack. - - Appropriate treatment with anticoagulants is permitted. * Ongoing cardiac dysrhythmias of NCI CTCAE Grade \>=2, uncontrolled atrial fibrillation of any grade, or QTc interval \>470 msec. * Pregnancy or breastfeeding. * Use of drugs or foods that are known potent CYP3A4 inducers/inhibitors Concurrent use of drugs that are CYP3A4 substrates with narrow therapeutic indices. * Known HIV infection * Known interstitial lung disease or interstitial fibrosis * Other severe acute or chronic medical conditions (including severe gastrointestinal conditions such as diarrhea or ulcer) or psychiatric conditions, or laboratory abnormalities that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration, and which would, therefore, make the patient inappropriate for entry into this study
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

intervention Names
Drug: treatment
label
A
type
EXPERIMENTAL
intervention Names
Drug: treatment
label
B
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
A
description
crizotinib 250mg orally continuous twice daily dosing
name
treatment
type
DRUG
arm Group Labels
B
description
pemetrexed 500mg/m2 IV day 1 plus cisplatin 75mg/m2 IV day 1 every 21 days OR pemetrexed 500mg/m2 IV day 1 plus carboplatin AUC 5 or 6 day 1 every 21 days investigator's choice
name
treatment
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 343
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
PFS was defined as the time from the date of randomization in study until the date of first documented objective tumor progression (according to RECIST v1.1 as determined by IRR) or death (due to any cause), whichever occurred first. PFS (in months) was calculated as (first event date - randomization date +1)/30.44. Objective progression was defined as a 20 percent (%) increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 millimeter (mm) or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions.
measure
Progression-Free Survival (PFS) Based on IRR
time Frame
Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)

secondary Outcomes

description
OS (in months) was defined as the duration from start of study treatment to date of death due to any cause. OS = (date of death minus the date of randomization of study medication plus 1) divided by 30.4. For participants who were alive, overall survival was censored on last date the participants were known to be alive.
measure
Overall Survival (OS)
time Frame
From randomization to death or last date known alive for those not known to have died (up to 72 months)
description
Overall survival probability at Month 12 and 18 was defined as the probability of overall survival at 12 and 18 months respectively, where the OS was defined as the duration from date of randomization to date of death due to any cause. The survival probability was estimated using the Kaplan-Meier method.
measure
Overall Survival Probability at Month 12 and 18
time Frame
Month 12, 18
description
ORR was defined as percentage of participants with complete response (CR) or partial response (PR) according to RECIST v1.1 determined by IRR. CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions and disappearance of all non-target lesions. PR was defined as greater than or equal to (\>=) 30% decrease taking as reference the baseline sum of lesion dimensions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No clear progression of non-target disease. No new lesions.
measure
Objective Response Rate (ORR): Percentage of Participants With Objective Response as Assessed by IRR
time Frame
Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)
description
DR: time from first documentation of objective tumor response (CR or PR) to first documentation of PD or death due to any cause, whichever occurred first as per RECIST v1.1 determined by IRR. CR: complete disappearance of all target and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions, disappearance of all non-target lesions. PR: \>=30% decrease taking as reference the baseline sum of lesion dimensions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all or target lesions. No clear progression of non-target disease. No new lesions. c) PD: 20 % increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 mm or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions.
measure
Duration of Response (DR) Based on IRR
time Frame
From objective response to date of progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)
description
TTR was defined as the time from randomization to first documentation of objective tumor response (CR or PR) according to RECIST v1.1 determined by IRR. CR: complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions and disappearance of all non-target lesions. PR: \>=30% decrease taking as reference the baseline sum of lesion dimensions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all or target lesions. No clear progression of non-target disease. No new lesions.
measure
Time to Tumor Response (TTR) Based on IRR
time Frame
Randomization to first documentation of objective tumor response (up to 35 months)
description
Disease control rate at week 12 is defined as the percent of participants with CR, PR, or stable disease (SD) at week 12 according to RECIST v1.1 determined by IRR. The best response of SD would be assigned if SD criteria was met at least once after randomization at a minimum interval of 6 weeks. CR: complete disappearance of all target lesions and non-target disease, with exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions and disappearance of all non-target lesions. PR: \>=30% decrease taking as reference the baseline sum of lesion dimensions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters. Short axis was used in sum for target nodes, while longest diameter was used in sum for all or target lesions. No clear progression of non-target disease. No new lesions.
measure
Percentage of Participants With Disease Control at Week 12 Based on IRR
time Frame
Week 12
description
TTP was defined as the time from the date of randomization to the date of the first documentation of objective tumor progression according to RECIST v1.1 determined by IRR. Objective tumor progression was defined as 20% increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 mm or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions. If tumor progression data included more than 1 date, the first date was used. TTP (in months) was calculated as (first event date - randomization date +1)/30.44.
measure
Time to Progression (TTP) Based on IRR
time Frame
Randomization to objective progression or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)
description
IC-TTP was defined similarly to TTP, but only considering intracranial disease (excluding extracranial disease) and the progression was determined based on either new brain metastases or progression of existing brain metastases. TTP was defined as the time from the date of randomization to the date of the first documentation of objective tumor progression according to RECIST v1.1 determined by IRR. Objective tumor progression was defined as 20% increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 mm or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions.
measure
Time to Intracranial Progression (IC-TTP) Based on IRR
time Frame
Randomization to objective intracranial progression or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)
description
EC-TTP was defined similarly to TTP, but only considering extracranial disease (excluding intracranial disease) and the progression was determined based on either new extracranial lesions or progression of existing extracranial lesions. TTP was defined as the time from the date of randomization to the date of the first documentation of objective tumor progression according to RECIST v1.1 determined by IRR. Objective tumor progression was defined as 20% increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 mm or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions.
measure
Time to Extracranial Progression (EC-TTP) Based on IRR
time Frame
Randomization to objective extracranial progression or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)
description
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose of study drug that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.
measure
Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
time Frame
Baseline up to follow up period (up to 72 months)
description
Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose of study drug that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator.
measure
Percentage of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
time Frame
Baseline up to follow up period (up to 72 months)
description
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to maximum severity grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Grade 1 =mild; Grade 2 =moderate; within normal limits, Grade 3 =severe or medically significant but not immediately life-threatening; Grade 4 =life-threatening or disabling; urgent intervention indicated; Grade 5 =death.
measure
Percentage of Participants With Adverse Events (AEs) According to Maximum Severity
time Frame
Baseline up to follow up period (up to 72 months)

Full study description

brief Summary: This study will evaluate the anti-cancer effects of crizotinib when compared with standard chemotherapy in patients with ALK positive lung cancer.

Source references

references

citation
Camidge DR, Kim EE, Usari T, Polli A, Lewis I, Wilner KD. Renal Effects of Crizotinib in Patients With ALK-Positive Advanced NSCLC. J Thorac Oncol. 2019 Jun;14(6):1077-1085. doi: 10.1016/j.jtho.2019.02.015. Epub 2019 Feb 26.
pmid
30822515
type
DERIVED
citation
Wilner KD, Usari T, Polli A, Kim EE. Comparison of cardiovascular effects of crizotinib and chemotherapy in ALK-positive advanced non-small-cell lung cancer. Future Oncol. 2019 Apr;15(10):1097-1103. doi: 10.2217/fon-2018-0869. Epub 2019 Jan 17.
pmid
30652510
type
DERIVED
citation
Solomon BJ, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Tang Y, Wilner KD, Blackhall F, Mok TS. Final Overall Survival Analysis From a Study Comparing First-Line Crizotinib Versus Chemotherapy in ALK-Mutation-Positive Non-Small-Cell Lung Cancer. J Clin Oncol. 2018 Aug 1;36(22):2251-2258. doi: 10.1200/JCO.2017.77.4794. Epub 2018 May 16.
pmid
29768118
type
DERIVED
citation
Yoneda KY, Scranton JR, Cadogan MA, Tassell V, Nadanaciva S, Wilner KD, Stollenwerk NS. Interstitial Lung Disease Associated With Crizotinib in Patients With Advanced Non-Small Cell Lung Cancer: Independent Review of Four PROFILE Trials. Clin Lung Cancer. 2017 Sep;18(5):472-479. doi: 10.1016/j.cllc.2017.03.004. Epub 2017 Mar 14.
pmid
28373069
type
DERIVED
citation
Solomon BJ, Cappuzzo F, Felip E, Blackhall FH, Costa DB, Kim DW, Nakagawa K, Wu YL, Mekhail T, Paolini J, Tursi J, Usari T, Wilner KD, Selaru P, Mok TS. Intracranial Efficacy of Crizotinib Versus Chemotherapy in Patients With Advanced ALK-Positive Non-Small-Cell Lung Cancer: Results From PROFILE 1014. J Clin Oncol. 2016 Aug 20;34(24):2858-65. doi: 10.1200/JCO.2015.63.5888. Epub 2016 Mar 28.
pmid
27022118
type
DERIVED
citation
Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Iyer S, Reisman A, Wilner KD, Tursi J, Blackhall F; PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014 Dec 4;371(23):2167-77. doi: 10.1056/NEJMoa1408440.
pmid
25470694
type
DERIVED
citation
Ou SH. Crizotinib: a drug that crystallizes a unique molecular subset of non-small-cell lung cancer. Expert Rev Anticancer Ther. 2012 Feb;12(2):151-62. doi: 10.1586/era.11.186.
pmid
22316363
type
DERIVED