計劃書編號BO28984
試驗已結束
2015-01-01 - 2024-11-26
Phase III
終止收納6
ICD-10C34.90
未明示側性支氣管或肺惡性腫瘤
ICD-10C34.91
右側支氣管或肺惡性腫瘤
ICD-10C34.92
左側支氣管或肺惡性腫瘤
ICD-10C7A.090
支氣管及肺惡性類癌
ICD-10Z51.12
來院接受抗腫瘤免疫療法
ICD-9162.9
支氣管及肺惡性腫瘤
在未曾接受治療、間變性淋巴瘤激酶陽性的晚期非小細胞肺癌患者中，比較ALECTINIB和CRIZOTINIB的隨機分組、多中心、第三期、開放標示試驗
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試驗申請者
台灣中外製藥股份有限公司
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試驗委託 / 贊助單位名稱
F. HOFFMANN-LA ROCHE LTD.
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臨床試驗規模
多國多中心
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更新日期
2026/04/01
試驗主持人及試驗醫院
實際收案人數
0 終止收納
實際收案人數
0 終止收納
適應症
Anaplastic lymphoma kinase�{positive (ALK-positive) non�{small cell lung cancer (NSCLC)
試驗目的
療效目的
本試驗的主要療效目的如下：
在未曾接受治療的間變性淋巴瘤激酶（anaplastic lymphoma kinase，ALK）陽性晚期非小細胞肺癌（non-small cell lung cancer，NSCLC）患者中，以試驗主持人評量之無惡化存活時間（progression-free survival，PFS）為指標，評估並比較alectinib和crizotinib的療效
安全性目的
本試驗之安全性目的如下：
評估alectinib相較於crizotinib的安全性和耐受性
藥品名稱
硬空膠囊劑
主成份
Alectinib
劑型
030
劑量
150
評估指標
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.
主要納入條件
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 �d 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 �d 100 �e 109/L
ANC �d 1500 cells/�尳
Hemoglobin �d 9.0 g/dL
Adequate renal function:
Calculated creatinine clearance at least 45 mL/min
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 and diagnosed incidentally at study baseline. If patients have neurological symptoms or signs due to CNS metastasis, patients need to complete whole brain radiation or gamma knife irradiation treatment at least 14 days before enrollment and 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 ( �d 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
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 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 �d 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 �d 100 �e 109/L
ANC �d 1500 cells/�尳
Hemoglobin �d 9.0 g/dL
Adequate renal function:
Calculated creatinine clearance at least 45 mL/min
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 and diagnosed incidentally at study baseline. If patients have neurological symptoms or signs due to CNS metastasis, patients need to complete whole brain radiation or gamma knife irradiation treatment at least 14 days before enrollment and 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 ( �d 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
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.
試驗計畫預計收納受試者人數
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台灣人數
18 人
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全球人數
286 人
