Clinical Trials List
Protocol NumberBO28984
NCT Number(ClinicalTrials.gov Identfier)NCT02075840
2015-01-01 - 2026-12-31
Phase III
Recruiting4
Terminated2
ICD-10C34.90
Malignant neoplasm of unspecified part of unspecified bronchus or lung
ICD-10C34.91
Malignant neoplasm of unspecified part of right bronchus or lung
ICD-10C34.92
Malignant neoplasm of unspecified part of left bronchus or lung
ICD-10C7A.090
Malignant carcinoid tumor of the bronchus and lung
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
RANDOMIZED, MULTICENTER, PHASE III, OPEN-LABEL STUDY OF ALECTINIB VERSUS CRIZOTINIB IN TREATMENT-NAÏVE ANAPLASTIC LYMPHOMA KINASE−POSITIVE ADVANCED NON−SMALL CELL LUNG CANCER
-
Trial Applicant
Chugai Pharma Taiwan Ltd.
-
Sponsor
F. Hoffmann-La Roche Ltd
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 蔡俊明 Division of Hematology & Oncology
- Chao-Hua Chiu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Wu-Chou Su Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
- Chien-Chung Lin Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
- Seu-Chun Yang Division of Hematology & Oncology
- Wen-Pin Su Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 黃世豪 Division of Thoracic Medicine
- 李忠恕 Division of Thoracic Medicine
- Chih-Hung Chen Division of Thoracic Medicine
- Shih-Hong Li Division of Thoracic Medicine
- Chien-Ying Liu Division of Thoracic Medicine
- 林倡華 Division of Thoracic Medicine
- 林倡葦 Division of Thoracic Medicine
- Wen-Cheng Chang Division of Thoracic Medicine
- Chih-Liang Wang Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Jih-Hsiang Lee Division of Hematology & Oncology
- 陳冠宇 Division of Hematology & Oncology
- 林宗哲 Division of Hematology & Oncology
- CHAO-CHI HO CHAO-CHI HO Division of Hematology & Oncology
- Chia-Chi Lin Division of Hematology & Oncology
- Chong-Jen Yu Division of Hematology & Oncology
- 廖唯昱 Division of Hematology & Oncology
- 林育麟 Division of Hematology & Oncology
- JIN-YUAN SHIH Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- KUO-HSUAN HSU Division of Thoracic Medicine
- JENG-SEN TSENG Division of Thoracic Medicine
- TSUNG -YING YANG Division of Thoracic Medicine
- 陳焜結 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chia-Hsiang Li Division of General Internal Medicine
- Chih-Yen Tu Division of General Internal Medicine
- 陳鴻仁 Division of General Internal Medicine
- Yu-Chao Lin Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
ADVANCED NON−SMALL CELL LUNG CANCER
Objectives
Efficacy Objectives
The primary efficacy objective for this study is as follows:
To evaluate and compare the efficacy of alectinib compared to crizotinib in patients with
treatment-naïve anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung
cancer (NSCLC), as measured by investigator-assessed progression-free survival (PFS)
The secondary efficacy objectives for this study are as follows:
To evaluate and compare the Objective Response Rate (ORR) and Duration of Response
(DOR)
To evaluate and compare the time to progression in the CNS on the basis of Independent
Review Committee (IRC) review of radiographs by Response Evaluation Criteria in Solid
Tumors (RECIST) v1.1 and Revised Assessment in Neuro Oncology (RANO) criteria, as
well as:
To evaluate CNS objective response rate (C-ORR) in patients with CNS metastases
who have measurable disease in the CNS at baseline
To assess CNS duration of response (C-DOR) in patients who have a CNS Objective
Response
To assess CNS progression rates (C-PR) at 6, 12, 18, and 24 months on the basis of
cumulative incidence
To evaluate and compare the PFS assessment by the IRC
To evaluate and compare the overall survival (OS)
Safety Objective
The safety objective for this study is as follows:
To evaluate the safety and tolerability of alectinib compared to crizotinib
Test Drug
RO5424802
Active Ingredient
Alectinib
Dosage Form
Capsules
Dosage
150
Endpoints
Efficacy Outcome Measures
The efficacy outcome measures for this study are as follows:
PFS, which is defined as the time from randomization to the first documented disease progression, as determined by the investigators (primary endpoint) or IRC (secondary endpoint) using RECIST v1.1 or death from any cause, whichever occurs first. Patients without an event will be censored at the last tumor assessment either during follow up or during study treatment. Patients with no post baseline assessments will be censored at the date of randomization.
ORR, which is defined as the percentage of patients who attain complete response (CR) or partial response (PR); response, as determined by the investigators using RECIST v1.1. Patients without any assessments will be regarded as non responders.
Time to CNS progression, which is defined as the time from randomization to the first occurrence of disease progression in the CNS as determined by IRC using RECIST v1.1 and RANO (separate assessments and analyses), as well as C-ORR in patients with CNS metastases who have measurable disease in the CNS at baseline, C-DOR in patients who have a CNS Objective Response, and C-PR at 6, 12, 18, and 24 months.
DOR, which is defined as the time from when response (CR or PR) was first documented to first documented disease progression or death (whichever occurs first). This will only be calculated for patients who have a best overall response of CR or PR. Patients who do not progress or die after they have had a response are censored at the date of their last tumor measurement.
OS, which is defined as the time from randomization to death from any cause. Patients without an event will be censored at the last date known to be alive. Patients without any follow up information will be censored at the date of randomization.
Safety Outcome Measures
The secondary safety outcome measures for this study are as follows:
Serious and non-serious adverse events
Safety laboratory tests values
Vital signs (blood pressure, heart rate), ECG
Physical examination
Pharmacokinetic Outcome Measures
The PK outcome measures for this study are as follows:
Sparse (pre-dose) PK samples for measurement of alectinib and its major metabolite(s) will be collected in all study patients receiving alectinib treatment
Serial/intensive PK sampling will be collected in a subset of consenting patients enrolled to receive alectinib treatment (approximately 10%�{15%, at least approximately n �� 20)
PK parameters will be determined as appropriate and where data allow:
The pharmacokinetics of alectinib (and metabolite[s], if appropriate) will be described, and the between-patient variability will be estimated using a population PK approach. The potential influence of covariates that contribute significantly to the between-patient differences in PK parameters of alectinib will also be explored and quantified.
Non compartmental analysis may be conducted in patients undergoing serial/intensive PK sample collection, as appropriate and where data allow.
Patient-Reported Outcome Measures
The PRO measures for this study are as follows:
EORTC QLQ-C30 and the EORTC QLQ LC13 to determine the impact of alectinib compared with crizotinib as measured by TTD in patient reported lung cancer symptoms (e.g., cough, dyspnea [single item and multi item scales], pain in chest, pain in arm/shoulder, fatigue).
The EORTC QLQ C30 and EORTC QLQ-LC13 to measure PROs of HRQoL, patient functioning, and side effects of therapy compared between patients treated with alectinib and those treated with crizotinib.
Exploratory Outcome Measures
The exploratory outcome measures for this study are as follows:
EQ-5D-3L to generate utility scores for use in economic models for reimbursement.
Total testosterone, albumin and SHBG to calculate free testosterone level, FSH, and LH, in blood to measure an onset of hypogonadism in adult men.
The FISH Vysis�� ALK Break Apart FISH Probe Kit (Abbott) to evaluate and compare efficacy and safety in patients with treatment-naïve NSCLC that is ALK-positive by FISH test.
Post progression tumor mutation status to study molecular mechanisms of resistance to ALK inhibitors.
ALK mutation status in plasma DNA to monitor efficacy and disease progression.
ALK fusion status in circulating tumor cells in blood.
The efficacy outcome measures for this study are as follows:
PFS, which is defined as the time from randomization to the first documented disease progression, as determined by the investigators (primary endpoint) or IRC (secondary endpoint) using RECIST v1.1 or death from any cause, whichever occurs first. Patients without an event will be censored at the last tumor assessment either during follow up or during study treatment. Patients with no post baseline assessments will be censored at the date of randomization.
ORR, which is defined as the percentage of patients who attain complete response (CR) or partial response (PR); response, as determined by the investigators using RECIST v1.1. Patients without any assessments will be regarded as non responders.
Time to CNS progression, which is defined as the time from randomization to the first occurrence of disease progression in the CNS as determined by IRC using RECIST v1.1 and RANO (separate assessments and analyses), as well as C-ORR in patients with CNS metastases who have measurable disease in the CNS at baseline, C-DOR in patients who have a CNS Objective Response, and C-PR at 6, 12, 18, and 24 months.
DOR, which is defined as the time from when response (CR or PR) was first documented to first documented disease progression or death (whichever occurs first). This will only be calculated for patients who have a best overall response of CR or PR. Patients who do not progress or die after they have had a response are censored at the date of their last tumor measurement.
OS, which is defined as the time from randomization to death from any cause. Patients without an event will be censored at the last date known to be alive. Patients without any follow up information will be censored at the date of randomization.
Safety Outcome Measures
The secondary safety outcome measures for this study are as follows:
Serious and non-serious adverse events
Safety laboratory tests values
Vital signs (blood pressure, heart rate), ECG
Physical examination
Pharmacokinetic Outcome Measures
The PK outcome measures for this study are as follows:
Sparse (pre-dose) PK samples for measurement of alectinib and its major metabolite(s) will be collected in all study patients receiving alectinib treatment
Serial/intensive PK sampling will be collected in a subset of consenting patients enrolled to receive alectinib treatment (approximately 10%�{15%, at least approximately n �� 20)
PK parameters will be determined as appropriate and where data allow:
The pharmacokinetics of alectinib (and metabolite[s], if appropriate) will be described, and the between-patient variability will be estimated using a population PK approach. The potential influence of covariates that contribute significantly to the between-patient differences in PK parameters of alectinib will also be explored and quantified.
Non compartmental analysis may be conducted in patients undergoing serial/intensive PK sample collection, as appropriate and where data allow.
Patient-Reported Outcome Measures
The PRO measures for this study are as follows:
EORTC QLQ-C30 and the EORTC QLQ LC13 to determine the impact of alectinib compared with crizotinib as measured by TTD in patient reported lung cancer symptoms (e.g., cough, dyspnea [single item and multi item scales], pain in chest, pain in arm/shoulder, fatigue).
The EORTC QLQ C30 and EORTC QLQ-LC13 to measure PROs of HRQoL, patient functioning, and side effects of therapy compared between patients treated with alectinib and those treated with crizotinib.
Exploratory Outcome Measures
The exploratory outcome measures for this study are as follows:
EQ-5D-3L to generate utility scores for use in economic models for reimbursement.
Total testosterone, albumin and SHBG to calculate free testosterone level, FSH, and LH, in blood to measure an onset of hypogonadism in adult men.
The FISH Vysis�� ALK Break Apart FISH Probe Kit (Abbott) to evaluate and compare efficacy and safety in patients with treatment-naïve NSCLC that is ALK-positive by FISH test.
Post progression tumor mutation status to study molecular mechanisms of resistance to ALK inhibitors.
ALK mutation status in plasma DNA to monitor efficacy and disease progression.
ALK fusion status in circulating tumor cells in blood.
Inclution Criteria
Inclusion Criteria
Patients must meet the following criteria for study entry:
Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not
amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive
as assessed by the Ventana IHC test. Sufficient tumor tissue to perform ALK IHC and ALK
FISH is required. Both tests will be performed at designated central laboratories.
Age 18 years old.
Life expectancy of at least 12 weeks.
ECOG PS of 0-2.
Patients had no prior systemic treatment for advanced or recurrent (Stage IIIB not
amenable for multimodality treatment) or metastatic (Stage IV) NSCLC.
Adequate hematologic function:
Platelet count 100 109
/L
ANC 1500 cells/L
Hemoglobin 9.0 g/dL
Adequate renal function:
An estimated glomerular filtration rate (eGFR) calculated using the
Modification of Diet in Renal Disease equation of at least 45 mL/min/1.73 m2
Patients must have recovered from effects of any major surgery or significant traumatic
injury at least 28 days before the first dose of study treatment.
Measurable disease (by RECIST v1.1) prior to the administration of study treatment.
Prior brain or leptomeningeal metastases allowed if asymptomatic (e.g., diagnosed
incidentally at study baseline). Asymptomatic CNS lesions might be treated at the
discretion of the investigator as per local clinical practice. If patients have
neurological symptoms or signs due to CNS metastasis, patients need to complete whole
brain radiation or gamma knife irradiation treatment. In all cases, radiation treatment
must be completed at least 14 days before enrollment and patients must be clinically
stable.
For all females of childbearing potential, a negative pregnancy test must be obtained within
3 days before starting study treatment.
For women who are not postmenopausal ( 12 months of non-therapy-induced amenorrhea)
or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or
use single or combined contraceptive methods that result in a failure rate of 1% per year
during the treatment period and for at least 3 months after the last dose of study drug.
Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation
methods) and withdrawal are not acceptable methods of contraception. Examples of
non-hormonal contraceptive methods with a failure rate of 1% per year include tubal
ligation, male sterilization, hormonal implants, established, proper use of combined oral or
injected hormonal contraceptives, and certain intrauterine devices. Alternatively, two
methods (e.g., two barrier methods such as a condom and a cervical cap) may be
combined to achieve a failure rate 1% per year. Barrier methods must always be
supplemented with the use of a spermicide.
For men: agreement to remain abstinent or use a condom plus an additional contraceptive
method that together result in a failure rate of 1% per year during the treatment period
and for at least 3 months after the last dose of study drug. Abstinence is only acceptable if
it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g.,
calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not
acceptable methods of contraception.
Able and willing to provide written informed consent prior to performing any study related
procedures and to comply with the study protocol, including patients must be willing and
able to use the electronic patient-reported outcome device.
Patients must meet the following criteria for study entry:
Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not
amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive
as assessed by the Ventana IHC test. Sufficient tumor tissue to perform ALK IHC and ALK
FISH is required. Both tests will be performed at designated central laboratories.
Age 18 years old.
Life expectancy of at least 12 weeks.
ECOG PS of 0-2.
Patients had no prior systemic treatment for advanced or recurrent (Stage IIIB not
amenable for multimodality treatment) or metastatic (Stage IV) NSCLC.
Adequate hematologic function:
Platelet count 100 109
/L
ANC 1500 cells/L
Hemoglobin 9.0 g/dL
Adequate renal function:
An estimated glomerular filtration rate (eGFR) calculated using the
Modification of Diet in Renal Disease equation of at least 45 mL/min/1.73 m2
Patients must have recovered from effects of any major surgery or significant traumatic
injury at least 28 days before the first dose of study treatment.
Measurable disease (by RECIST v1.1) prior to the administration of study treatment.
Prior brain or leptomeningeal metastases allowed if asymptomatic (e.g., diagnosed
incidentally at study baseline). Asymptomatic CNS lesions might be treated at the
discretion of the investigator as per local clinical practice. If patients have
neurological symptoms or signs due to CNS metastasis, patients need to complete whole
brain radiation or gamma knife irradiation treatment. In all cases, radiation treatment
must be completed at least 14 days before enrollment and patients must be clinically
stable.
For all females of childbearing potential, a negative pregnancy test must be obtained within
3 days before starting study treatment.
For women who are not postmenopausal ( 12 months of non-therapy-induced amenorrhea)
or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or
use single or combined contraceptive methods that result in a failure rate of 1% per year
during the treatment period and for at least 3 months after the last dose of study drug.
Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation
methods) and withdrawal are not acceptable methods of contraception. Examples of
non-hormonal contraceptive methods with a failure rate of 1% per year include tubal
ligation, male sterilization, hormonal implants, established, proper use of combined oral or
injected hormonal contraceptives, and certain intrauterine devices. Alternatively, two
methods (e.g., two barrier methods such as a condom and a cervical cap) may be
combined to achieve a failure rate 1% per year. Barrier methods must always be
supplemented with the use of a spermicide.
For men: agreement to remain abstinent or use a condom plus an additional contraceptive
method that together result in a failure rate of 1% per year during the treatment period
and for at least 3 months after the last dose of study drug. Abstinence is only acceptable if
it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g.,
calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not
acceptable methods of contraception.
Able and willing to provide written informed consent prior to performing any study related
procedures and to comply with the study protocol, including patients must be willing and
able to use the electronic patient-reported outcome device.
Exclusion Criteria
Exclusion Criteria
Patients who meet any of the following criteria will be excluded from study entry:
Patients with a previous malignancy within the past 3 years are excluded (other than curatively treated basal cell carcinoma of the skin, early gastrointestinal (GI) cancer by endoscopic resection, in situ carcinoma of the cervix, or any cured cancer that is considered to have no impact in PFS and OS for the current NSCLC).
Any GI disorder that may affect absorption of oral medications, such as mal absorption syndrome or status post-major bowel resection.
Liver disease characterized by:
ALT or AST �� 3 �e ULN (�d 5 �e ULN for patients with concurrent liver metastasis) confirmed on two consecutive measurements
OR
Impaired excretory function (e.g., hyperbilirubinemia) or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices
OR
Acute viral or active autoimmune, alcoholic, or other types of hepatitis
National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) Grade 3 or higher toxicities due to any prior therapy (e.g., radiotherapy) (excluding alopecia), which have not shown improvement and are strictly considered to interfere with current study medication.
History of organ transplant.
Co-administration of anti-cancer therapies other than those administered in this study.
Patients with baseline QTc �� 470 ms or patients with symptomatic bradycardia �� 45 beats per minute.
Administration of strong/potent cytochrome P4503A inhibitors or inducers within 14 days prior to the first dose of study treatment and while on treatment with alectinib or crizotinib except for oral corticosteroids up to 20 mg of prednisolone equivalent per day
Administration of agents with potential QT interval prolonging effects within 14 days prior to the first administration of study drug and while on treatment.
History of hypersensitivity to any of the additives in the alectinib drug formulation (lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, hydroxypropyl cellulose, sodium lauryl sulfate [SLS], magnesium stearate).
History of hypersensitivity to any of the additives in the crizotinib drug formulation (silica, colloidal anhydrous cellulose, microcrystalline calcium hydrogen phosphate, anhydrous sodium starch glycolate, magnesium stearate).
Pregnant or lactating women.
Known HIV positivity or AIDS-related illness.
Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or the absorption of oral medications or that would, in the opinion of the Principal Investigator, pose an unacceptable risk to the patient in this study.
Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the patient before trial entry.
Patients who meet any of the following criteria will be excluded from study entry:
Patients with a previous malignancy within the past 3 years are excluded (other than curatively treated basal cell carcinoma of the skin, early gastrointestinal (GI) cancer by endoscopic resection, in situ carcinoma of the cervix, or any cured cancer that is considered to have no impact in PFS and OS for the current NSCLC).
Any GI disorder that may affect absorption of oral medications, such as mal absorption syndrome or status post-major bowel resection.
Liver disease characterized by:
ALT or AST �� 3 �e ULN (�d 5 �e ULN for patients with concurrent liver metastasis) confirmed on two consecutive measurements
OR
Impaired excretory function (e.g., hyperbilirubinemia) or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices
OR
Acute viral or active autoimmune, alcoholic, or other types of hepatitis
National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) Grade 3 or higher toxicities due to any prior therapy (e.g., radiotherapy) (excluding alopecia), which have not shown improvement and are strictly considered to interfere with current study medication.
History of organ transplant.
Co-administration of anti-cancer therapies other than those administered in this study.
Patients with baseline QTc �� 470 ms or patients with symptomatic bradycardia �� 45 beats per minute.
Administration of strong/potent cytochrome P4503A inhibitors or inducers within 14 days prior to the first dose of study treatment and while on treatment with alectinib or crizotinib except for oral corticosteroids up to 20 mg of prednisolone equivalent per day
Administration of agents with potential QT interval prolonging effects within 14 days prior to the first administration of study drug and while on treatment.
History of hypersensitivity to any of the additives in the alectinib drug formulation (lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, hydroxypropyl cellulose, sodium lauryl sulfate [SLS], magnesium stearate).
History of hypersensitivity to any of the additives in the crizotinib drug formulation (silica, colloidal anhydrous cellulose, microcrystalline calcium hydrogen phosphate, anhydrous sodium starch glycolate, magnesium stearate).
Pregnant or lactating women.
Known HIV positivity or AIDS-related illness.
Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or the absorption of oral medications or that would, in the opinion of the Principal Investigator, pose an unacceptable risk to the patient in this study.
Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the patient before trial entry.
The Estimated Number of Participants
-
Taiwan
18 participants
-
Global
286 participants
