Clinical Trials List
Protocol NumberBrigatinib-3001
NCT Number(ClinicalTrials.gov Identfier)NCT03596866
2019-01-01 - 2025-01-31
Phase III
Recruiting7
ICD-9162.8
Malignant neoplasm of other parts of bronchus or lung
A Phase 3 Randomized Open-label Study of Brigatinib (ALUNBRIGTM) Versus Alectinib (ALECENSA) in Advanced Anaplastic Lymphoma Kinase-Positive Non--Small-Cell Lung Cancer Patients Who Have Progressed on Crizotinib
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Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
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Sponsor
ARIAD Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chih-Hung Chen Division of Thoracic Medicine
- 邱立忠 無
- Chih-Hung Chen 無
- Ping-Chih Hsu 無
- 枋岳甫 無
- Chien-Ying Liu 無
- Chih-Hsi Kuo 無
- 林定佑 無
- Wen-Cheng Chang 無
- 柯皓文 無
- Chih-Liang Wang 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Jih-Hsiang Lee Division of Hematology & Oncology
- CHAO-CHI HO CHAO-CHI HO Division of Hematology & Oncology
- 廖唯昱 Division of Hematology & Oncology
- 吳尚俊 無
- Chia-Chi Lin Division of Hematology & Oncology
- 林宗哲 Division of Hematology & Oncology
- 蔡子修 Division of Hematology & Oncology
- 楊景堯 Division of Hematology & Oncology
- JIN-YUAN SHIH Division of Hematology & Oncology
- 陳冠宇 Division of Hematology & Oncology
- 徐偉勛 Division of Hematology & Oncology
- YEN-TING LIN Division of Hematology & Oncology
- Chong-Jen Yu Division of Hematology & Oncology
- 廖斌志 Division of Hematology & Oncology
- 林育麟 Division of Hematology & Oncology
- 許嘉林 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- Jui-Ying Lee 無
- Ying-Ming Tsai Tsai 無
- 郭家佑 無
- 李玫萱 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
non-small cell lung cancer (NSCLC)
Objectives
Primary Objective:
To compare the efficacy of brigatinib to that of alectinib in patients with ALK+ locally advanced or metastatic NSCLC who have progressed on crizotinib as evidenced by progression-free survival (PFS) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Test Drug
Brigatinib
Active Ingredient
Brigatinib
Dosage Form
film coated tablets
film coated tablets
film coated tablets
film coated tablets
film coated tablets
Dosage
30
90
180
90
180
Endpoints
Main evaluation indicators:
The main evaluation indicator is PFS, which is evaluated by the blinded Independent Review Committee (BIRC) based on RECIST Version 1.1.
Key and secondary evaluation indicators:
1. The elapsed time before iPD is evaluated by BIRC based on the revised RECIST version 1.1.
2. Overall survival (OS).
Other secondary evaluation indicators:
1. ORR, evaluated by the trial leader and BIRC based on RECIST Version 1.1.
2. The time elapsed before the reaction appears will be evaluated by the trial host and BIRC.
3. DOR, evaluated by the trial leader and BIRC.
4. iORR is evaluated by BIRC based on the revised RECIST version 1.1 (as described in the test plan and BIRC regulations).
5. iDOR, evaluated by BIRC based on revised RECIST version 1.1.
6. HRQoL, using EORTC QLQ-C30 (version 3.0) and EORTC QLQ-LC13 to collect overall health status/quality of life and other functional and symptom areas for evaluation.
Safety evaluation index:
The safety assessment items will include physical and laboratory tests, vital signs and electrocardiogram. Adverse events will be classified according to NCI CTCAE version 4.03.
Exploratory evaluation indicators:
1. The efficacy of CNS evaluated by BIRC based on the RANO-BM criteria (iORR, iDOR, and elapsed time before iPD).
2. The molecular determinants of the efficacy and safety of Brigatinib and Alectinib.
3. HRQoL measured by EuroQol-5 oriented -5 level (EQ-5D-5L) questionnaire.
4. The EORTC Quality of Life Brain Cancer Unit (QLQ-BN20) project used to assess the morbidity associated with CNS symptoms.
5. Assess the utilization of medical resources.
The main evaluation indicator is PFS, which is evaluated by the blinded Independent Review Committee (BIRC) based on RECIST Version 1.1.
Key and secondary evaluation indicators:
1. The elapsed time before iPD is evaluated by BIRC based on the revised RECIST version 1.1.
2. Overall survival (OS).
Other secondary evaluation indicators:
1. ORR, evaluated by the trial leader and BIRC based on RECIST Version 1.1.
2. The time elapsed before the reaction appears will be evaluated by the trial host and BIRC.
3. DOR, evaluated by the trial leader and BIRC.
4. iORR is evaluated by BIRC based on the revised RECIST version 1.1 (as described in the test plan and BIRC regulations).
5. iDOR, evaluated by BIRC based on revised RECIST version 1.1.
6. HRQoL, using EORTC QLQ-C30 (version 3.0) and EORTC QLQ-LC13 to collect overall health status/quality of life and other functional and symptom areas for evaluation.
Safety evaluation index:
The safety assessment items will include physical and laboratory tests, vital signs and electrocardiogram. Adverse events will be classified according to NCI CTCAE version 4.03.
Exploratory evaluation indicators:
1. The efficacy of CNS evaluated by BIRC based on the RANO-BM criteria (iORR, iDOR, and elapsed time before iPD).
2. The molecular determinants of the efficacy and safety of Brigatinib and Alectinib.
3. HRQoL measured by EuroQol-5 oriented -5 level (EQ-5D-5L) questionnaire.
4. The EORTC Quality of Life Brain Cancer Unit (QLQ-BN20) project used to assess the morbidity associated with CNS symptoms.
5. Assess the utilization of medical resources.
Inclution Criteria
Main conditions for inclusion:
A male or female who is 18 years of age or older or reaches the local legal age of majority.
Patients with stage IIIB (locally advanced or recurrent) or stage IV NSCLC confirmed by histology or cytology.
Must meet one of the following conditions:
– Has a record of anaplastic lymphoma stimulated 酶 (ALK gene) recombination, based on the ALK Break-Apart fluorescent original hybridization probe kit (Vysis ALK Break-Apart fluorescence in situ hybridization [fluorescence in situ hybridization] , FISH] Probe Kit) or Ventana ALK (D5F3) CDx analysis method or FoundationOne CDx produced by Foundation Medicine is judged as a positive result.
– Have a record of ALK gene recombination detected by different tests, and be able to provide tumor samples to the central laboratory. (Note: It is not necessary to obtain the ALK gene recombination test result of the central laboratory before random assignment.)
The trial host or attending physician judged that the disease worsened while using Crizotinib. (Note: Crzotinib does not need to be the last treatment the patient receives. The patient may have received chemotherapy as their last systemic anticancer therapy.)
Treat with Crizotinib for at least 4 weeks before the disease worsens.
-Never used ALK inhibitors other than Crizotinib.
Has not previously used more than 2 courses of systemic anticancer therapy for locally advanced or metastatic conditions (other than Crizotinib). (Note: Systemic anti-cancer therapy is counted if it is administered for at least 1 complete course. New anti-cancer agents used as maintenance therapy will be counted as a new course of treatment. If disease deterioration/recurrence occurs in neoadjuvant or Within 12 months after the completion of adjuvant systemic anticancer therapy, the neoadjuvant or adjuvant therapy will be regarded as a previous course of treatment.) *If the maintenance therapy contains the drugs used in the course of treatment before the maintenance, then Systemic therapy followed by maintenance therapy will be regarded as a course of treatment.
-Eastern Cooperative Oncology Group (Eastern Cooperative Oncology Group) fitness status is 0 to 2.
-According to RECIST Version 1.1, there is at least 1 measurable (ie index) lesion.
-Has been restored from previous anticancer therapy-related toxicity to a level less than or equal to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03≤1 . (Note: If it is judged to be irreversible, it can be included in treatment-related hair loss or peripheral neuropathy of grade> 1.)
-Sufficient organ function, according to the following judgment:
-Total bilirubin ≤1.5 times the upper limit of normal (ULN).
– The estimated value of glomerular filtration rate ≥30 mL/min/1.73 m2, calculated using the kidney disease diet adjustment formula.
-Alanine transamine enzyme/aspartic acid transamine enzyme≤2.5 × ULN; if there is liver metastasis, ≤5 × ULN is acceptable.
– Serum lipids enzyme&≤1.5 × ULN.
-Platelet count ≥75 × 109/L.
– Heme≥9 g/dL.
– Absolute neutrophil count ≥ 1.5 × 109/L.
Appropriate venous access for blood sampling (including PK and laboratory safety testing) required for the test.
Willing and able to cooperate with scheduled visits and trial procedures.
; For female patients with fertility, the pregnancy test before random assignment was negative.
; For female and male patients with fertility, agree to use highly effective contraceptive methods with their sexual partners during the medication period and at least 120 days after the end of Brigatinib or Alectinib treatment.
A male or female who is 18 years of age or older or reaches the local legal age of majority.
Patients with stage IIIB (locally advanced or recurrent) or stage IV NSCLC confirmed by histology or cytology.
Must meet one of the following conditions:
– Has a record of anaplastic lymphoma stimulated 酶 (ALK gene) recombination, based on the ALK Break-Apart fluorescent original hybridization probe kit (Vysis ALK Break-Apart fluorescence in situ hybridization [fluorescence in situ hybridization] , FISH] Probe Kit) or Ventana ALK (D5F3) CDx analysis method or FoundationOne CDx produced by Foundation Medicine is judged as a positive result.
– Have a record of ALK gene recombination detected by different tests, and be able to provide tumor samples to the central laboratory. (Note: It is not necessary to obtain the ALK gene recombination test result of the central laboratory before random assignment.)
The trial host or attending physician judged that the disease worsened while using Crizotinib. (Note: Crzotinib does not need to be the last treatment the patient receives. The patient may have received chemotherapy as their last systemic anticancer therapy.)
Treat with Crizotinib for at least 4 weeks before the disease worsens.
-Never used ALK inhibitors other than Crizotinib.
Has not previously used more than 2 courses of systemic anticancer therapy for locally advanced or metastatic conditions (other than Crizotinib). (Note: Systemic anti-cancer therapy is counted if it is administered for at least 1 complete course. New anti-cancer agents used as maintenance therapy will be counted as a new course of treatment. If disease deterioration/recurrence occurs in neoadjuvant or Within 12 months after the completion of adjuvant systemic anticancer therapy, the neoadjuvant or adjuvant therapy will be regarded as a previous course of treatment.) *If the maintenance therapy contains the drugs used in the course of treatment before the maintenance, then Systemic therapy followed by maintenance therapy will be regarded as a course of treatment.
-Eastern Cooperative Oncology Group (Eastern Cooperative Oncology Group) fitness status is 0 to 2.
-According to RECIST Version 1.1, there is at least 1 measurable (ie index) lesion.
-Has been restored from previous anticancer therapy-related toxicity to a level less than or equal to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03≤1 . (Note: If it is judged to be irreversible, it can be included in treatment-related hair loss or peripheral neuropathy of grade> 1.)
-Sufficient organ function, according to the following judgment:
-Total bilirubin ≤1.5 times the upper limit of normal (ULN).
– The estimated value of glomerular filtration rate ≥30 mL/min/1.73 m2, calculated using the kidney disease diet adjustment formula.
-Alanine transamine enzyme/aspartic acid transamine enzyme≤2.5 × ULN; if there is liver metastasis, ≤5 × ULN is acceptable.
– Serum lipids enzyme&≤1.5 × ULN.
-Platelet count ≥75 × 109/L.
– Heme≥9 g/dL.
– Absolute neutrophil count ≥ 1.5 × 109/L.
Appropriate venous access for blood sampling (including PK and laboratory safety testing) required for the test.
Willing and able to cooperate with scheduled visits and trial procedures.
; For female patients with fertility, the pregnancy test before random assignment was negative.
; For female and male patients with fertility, agree to use highly effective contraceptive methods with their sexual partners during the medication period and at least 120 days after the end of Brigatinib or Alectinib treatment.
Exclusion Criteria
Main exclusion conditions:
Control (Crizotinib) group participating in the AP26113-13-301 trial (ALTA 1L)
Receive Crizotinib within 7 days of random assignment.
Have a history of interstitial lung disease, drug-related pneumonia, or radiation pneumonia, or have these diseases during the baseline period.
-Have uncontrolled high blood pressure. When entering the trial, patients with hypertension should receive treatment to control their blood pressure.
Within 14 days before random assignment, receive systemic treatment with a strong cytochrome P-450 (CYP) 3A inhibitor, a moderate inhibitor of CYP3A, a strong CYP3A inducer, or a moderate inducer of CYP3A.
Receive treatment with any investigational systemic anticancer agents within 14 days or 5 half-lives (whichever is longer) before random assignment.
Receive chemotherapy or radiotherapy within 14 days of random assignment, except for stereotactic radiosurgery or whole body stereotactic radiotherapy.
Receive anti-cancer monoclonal antibodies within 30 days of random assignment.
Underwent major surgery within 30 days of random assignment. It can be incorporated into minor surgical procedures, such as catheter placement or minimally invasive tissue sectioning.
Patients with symptomatic CNS metastases (parenchymal or pia mater) at the time of screening (Patients with asymptomatic brain metastases, or patients with stable symptoms within 7 days before randomization without the need to increase corticosteroid doses to control symptoms, will be given Included).
(Note: If the patient's neurological symptoms or signs worsen due to CNS metastasis, the patient needs to complete local treatment and be neurologically stable 7 days before randomization [No need to increase corticosteroid dose or use anticonvulsants].)
• Currently suffering from spinal cord compression (symptomatic or asymptomatic, and detected by radiographic imaging). Patients with leptomeningeal disease but no spinal cord compression are allowed.
Suffer from major, uncontrolled or active cardiovascular diseases, including but not limited to the following diseases:
1. Myocardial infarction occurred within 6 months before random assignment.
2. Unstable angina occurred within 6 months before random assignment.
3. New York Heart Association Grade III or IV heart failure occurred within 6 months before random assignment.
4. A history of clinically significant atrial arrhythmia (including clinically significant bradyarrhythmia), as judged by the attending physician.
5. There is a history of any clinically significant ventricular arrhythmia.
A cerebrovascular accident or transient ischemic attack occurred within 6 months before the first dose of the test drug.
Suffer from malabsorption syndrome or other gastrointestinal diseases or conditions that may affect the oral absorption of the test drug.
Suffering from ongoing or active infections, including but not limited to the need for intravenous antibiotics.
Known medical history of human immunodeficiency virus (HIV) infection; no medical history requires no testing.
Known positive for hepatitis B surface antigen, or known or suspected active hepatitis C infection.
As determined by the trial host, any serious medical condition or mental illness may endanger the safety of the patient or interfere with the completion of the treatment according to this trial plan.
Known or suspected allergy to Brigatinib or Alectinib or its excipients.
Life-threatening diseases not related to cancer.
Control (Crizotinib) group participating in the AP26113-13-301 trial (ALTA 1L)
Receive Crizotinib within 7 days of random assignment.
Have a history of interstitial lung disease, drug-related pneumonia, or radiation pneumonia, or have these diseases during the baseline period.
-Have uncontrolled high blood pressure. When entering the trial, patients with hypertension should receive treatment to control their blood pressure.
Within 14 days before random assignment, receive systemic treatment with a strong cytochrome P-450 (CYP) 3A inhibitor, a moderate inhibitor of CYP3A, a strong CYP3A inducer, or a moderate inducer of CYP3A.
Receive treatment with any investigational systemic anticancer agents within 14 days or 5 half-lives (whichever is longer) before random assignment.
Receive chemotherapy or radiotherapy within 14 days of random assignment, except for stereotactic radiosurgery or whole body stereotactic radiotherapy.
Receive anti-cancer monoclonal antibodies within 30 days of random assignment.
Underwent major surgery within 30 days of random assignment. It can be incorporated into minor surgical procedures, such as catheter placement or minimally invasive tissue sectioning.
Patients with symptomatic CNS metastases (parenchymal or pia mater) at the time of screening (Patients with asymptomatic brain metastases, or patients with stable symptoms within 7 days before randomization without the need to increase corticosteroid doses to control symptoms, will be given Included).
(Note: If the patient's neurological symptoms or signs worsen due to CNS metastasis, the patient needs to complete local treatment and be neurologically stable 7 days before randomization [No need to increase corticosteroid dose or use anticonvulsants].)
• Currently suffering from spinal cord compression (symptomatic or asymptomatic, and detected by radiographic imaging). Patients with leptomeningeal disease but no spinal cord compression are allowed.
Suffer from major, uncontrolled or active cardiovascular diseases, including but not limited to the following diseases:
1. Myocardial infarction occurred within 6 months before random assignment.
2. Unstable angina occurred within 6 months before random assignment.
3. New York Heart Association Grade III or IV heart failure occurred within 6 months before random assignment.
4. A history of clinically significant atrial arrhythmia (including clinically significant bradyarrhythmia), as judged by the attending physician.
5. There is a history of any clinically significant ventricular arrhythmia.
A cerebrovascular accident or transient ischemic attack occurred within 6 months before the first dose of the test drug.
Suffer from malabsorption syndrome or other gastrointestinal diseases or conditions that may affect the oral absorption of the test drug.
Suffering from ongoing or active infections, including but not limited to the need for intravenous antibiotics.
Known medical history of human immunodeficiency virus (HIV) infection; no medical history requires no testing.
Known positive for hepatitis B surface antigen, or known or suspected active hepatitis C infection.
As determined by the trial host, any serious medical condition or mental illness may endanger the safety of the patient or interfere with the completion of the treatment according to this trial plan.
Known or suspected allergy to Brigatinib or Alectinib or its excipients.
Life-threatening diseases not related to cancer.
The Estimated Number of Participants
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Taiwan
23 participants
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Global
246 participants
