Clinical Trials List
Protocol NumberMYL-1402O-3001
2016-09-12 - 2019-12-05
Phase III
Terminated6
ICD-10C34
Malignant neoplasm of bronchus and lung
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
Multicenter, Double-Blind, Randomized, Parallel-Group Study to Assess the Efficacy and Safety of MYL-1402O Compared With Avastin®, in the First-line Treatment of Patients with Stage IV Non-Squamous Non-Small Cell Lung Cancer
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Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
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Sponsor
Mylan GmbH
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 陳焜結 Division of Thoracic Medicine
- KUO-HSUAN HSU Division of Thoracic Medicine
- TSUNG -YING YANG Division of Thoracic Medicine
- JENG-SEN TSENG Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 吳俊廷 Division of Thoracic Medicine
- 陳俊榮 Division of Thoracic Medicine
- 許棨逵 Division of Thoracic Medicine
- 謝坤洲 Division of Thoracic Surgery
- 邱建通 Division of General Internal Medicine
- 陳鍾岳 Division of Thoracic Medicine
- 鄭裕仁 Division of Thoracic Surgery
- 李和昇 Division of Thoracic Medicine
- 賴永發 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Ying-Ming Tsai Tsai Division of Thoracic Medicine
- 李玫萱 Division of Thoracic Medicine
- 郭家佑 Division of Thoracic Medicine
- Jui-Ying Lee Division of Thoracic Surgery
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
NSCLC
Objectives
The overall response rate (ORR) of MYL-1402O and Avastin was compared for the first-line treatment of patients with stage IV nsNSCLC combined with CP chemotherapy in the first 18 weeks.
Test Drug
MYL-1402O
Active Ingredient
MYL-1402O / Bevacizumab
Dosage Form
IV
Dosage
100mg/4mL(25mg/mL); 400mg/16mL(25mg/mL)
Endpoints
main target:
For the first-line treatment of stage IV nsNSCLC patients with CP chemotherapy in the first 18 weeks, the overall response rate (ORR) of MYL-1402O and Avastin was compared.
For the first-line treatment of stage IV nsNSCLC patients with CP chemotherapy in the first 18 weeks, the overall response rate (ORR) of MYL-1402O and Avastin was compared.
Inclution Criteria
Subject inclusion conditions
If you meet all of the following conditions, you are eligible to be included in this trial:
1. Ability to understand oral and/or written instructions, provide written informed consent, and be able and agree to comply with the requirements of the test plan.
2. A male or female who is at least 18 years old when signing the Subject Consent Form (ICF). (Participants participating in this trial in Taiwan must be over 20 years old.)
3. There is a record of angiographic diagnosis of stage IV unresectable, recurrent or metastatic non-squamous non-small cell lung cancer (nsNSCLC).
4. Histological or cytological diagnosis record of advanced nsNSCLC, and negative or unknown sensitive epithelial cell growth factor receptor (EGFR) gene mutation, and negative or unknown echinoderm microtubule binding protein 4-anaplastic Lymphoma stimulated enzyme (EML4-ALK) gene recombination.
5. According to the definition of the solid tumor response assessment criteria (RECIST1.1), a measurable disease with at least 1 measurable lesion. Disease response assessment or evaluation should include all target lesions (up to 5) and non-target lesions (other measurable lesions, non-measurable lesions, non-evaluable lesions or evaluable lesions that are not target lesions) as defined in RECIST 1.1.
Please note: If bone metastases are found in the staging assessment and the area is outside the chest and abdomen, the tumor response assessment should include each non-target metastasis or multiple non-target bone metastases, and then X-ray examination, computer tomography (CT) should be performed as appropriate. ) Scan or MRI.
6. The ECOG Performance Status (PS) score of the United States East Coast Cancer Clinical Research Cooperative (ECOG) scale is 0 or 1.
7. The expected survival is at least 6 months.
8. Have not received any systemic treatment (except adjuvant chemotherapy) for the first-line treatment of advanced lung cancer before, and have been disease-free for at least 12 months from the time of surgery, and at least 6 months after the last dose of chemotherapy .
9. You may have received radiotherapy before, but the scope must involve less than 25% of the bone marrow, and it is not allowed to have received mediastinal radiation.
a. The previous radiotherapy must be completed at least 2 weeks before the 0th day of the first cycle.
b. The patient must have recovered from the acute toxicity associated with radiotherapy. Before the 0th day of cycle 1, radiation-related toxicity must have been restored to grade 1 (according to the National Cancer Institute's Common Terminology Standard for Adverse Events CTCAE; version 4.03).
10. There may be brain metastases, but the metastases must have been treated and considered stable. Treated and stable brain metastases are defined as:
a. After treatment for metastasis, there is no evidence of disease progression (PD) or bleeding.
b. In the baseline period, through clinical examination and post-treatment brain imaging (computerized tomography [CT] scan or magnetic resonance imaging [MRI]), it is determined that there is no need to continue using dexamethasone.
c. Anticonvulsants are allowed, but the dosage must be maintained (stable) at least 2 weeks before the patient signs the informed consent.
d. The treatment of brain metastases can include whole brain radiation, radiosurgery (Gamma Knife®, linear particle accelerator or equivalent treatment), or a combination of treatments deemed appropriate by the attending physician. All treatments for brain metastases must be completed at least 14 days before day 0 of cycle 1.
11. Determine good organ function according to the following indicators:
a. Bone marrow reserve capacity:
i. The number of white blood cells >=3×103/microliter (μL);
ii. The absolute number of neutrophils (sections and bands) >= 1.5×103/μl (μL);
iii. The number of platelets >=100×103/microliter (μL);
iv. Hemoglobin >=9.0 grams per deciliter (g/dL), and there is no blood transfusion at least 2 weeks before the 0th day of the first cycle.
b. Liver:
i. Total bilirubin <=1.5 times the upper limit of normal (ULN); except for the short-term increase of indirect bilirubin caused by Gilbert's syndrome;
ii. Alkaline phosphoric acid enzyme, alanine transamination enzyme and/or aspartic acid transamination enzyme <= 3 times the upper limit of normal (ULN). If it is not related to liver metastasis, further evaluation should be made for the significant concentration of alanine transamine enzyme or aspartic acid transamine enzyme to confirm viral hepatitis. (Note: It is permissible for the individual concentration of alkaline phosphate enzyme to increase by more than 3 times the upper limit of normal (ULN) due to bone metastasis.)
c. Kidney:
i. Creatinine clearance rate (CrCl) calculated according to the original Cockcroft-Gault formula calculated by body weight (CrCl) >= 45 ml/min (mL/min);
ii. Urine protein (tested with test paper): 0 or 1+. Only if the protein collected in the 24-hour urine is <2g, it can be included in >= 2+ patients.
12. Reproductive patients and their partners must use contraceptive methods during the entire trial period and 6 months after the trial is interrupted.
a. Reproductive patients must be willing to use two high-efficiency double-barrier contraceptive methods for contraception, or abstain from sex during the trial period.
i. In particular, female patients with fertility must continue and correctly use methods that have a failure rate of less than 1% per year, such as implants, injections, comprehensive oral contraceptives, uterine contraceptives, abstinence, or their partners The vas deferens has been ligated.
ii. Reproductive male patients (defined as men who have not undergone vasectomy) must use condoms with spermicide, and their female partners must use another effective method of contraception.
If you meet all of the following conditions, you are eligible to be included in this trial:
1. Ability to understand oral and/or written instructions, provide written informed consent, and be able and agree to comply with the requirements of the test plan.
2. A male or female who is at least 18 years old when signing the Subject Consent Form (ICF). (Participants participating in this trial in Taiwan must be over 20 years old.)
3. There is a record of angiographic diagnosis of stage IV unresectable, recurrent or metastatic non-squamous non-small cell lung cancer (nsNSCLC).
4. Histological or cytological diagnosis record of advanced nsNSCLC, and negative or unknown sensitive epithelial cell growth factor receptor (EGFR) gene mutation, and negative or unknown echinoderm microtubule binding protein 4-anaplastic Lymphoma stimulated enzyme (EML4-ALK) gene recombination.
5. According to the definition of the solid tumor response assessment criteria (RECIST1.1), a measurable disease with at least 1 measurable lesion. Disease response assessment or evaluation should include all target lesions (up to 5) and non-target lesions (other measurable lesions, non-measurable lesions, non-evaluable lesions or evaluable lesions that are not target lesions) as defined in RECIST 1.1.
Please note: If bone metastases are found in the staging assessment and the area is outside the chest and abdomen, the tumor response assessment should include each non-target metastasis or multiple non-target bone metastases, and then X-ray examination, computer tomography (CT) should be performed as appropriate. ) Scan or MRI.
6. The ECOG Performance Status (PS) score of the United States East Coast Cancer Clinical Research Cooperative (ECOG) scale is 0 or 1.
7. The expected survival is at least 6 months.
8. Have not received any systemic treatment (except adjuvant chemotherapy) for the first-line treatment of advanced lung cancer before, and have been disease-free for at least 12 months from the time of surgery, and at least 6 months after the last dose of chemotherapy .
9. You may have received radiotherapy before, but the scope must involve less than 25% of the bone marrow, and it is not allowed to have received mediastinal radiation.
a. The previous radiotherapy must be completed at least 2 weeks before the 0th day of the first cycle.
b. The patient must have recovered from the acute toxicity associated with radiotherapy. Before the 0th day of cycle 1, radiation-related toxicity must have been restored to grade 1 (according to the National Cancer Institute's Common Terminology Standard for Adverse Events CTCAE; version 4.03).
10. There may be brain metastases, but the metastases must have been treated and considered stable. Treated and stable brain metastases are defined as:
a. After treatment for metastasis, there is no evidence of disease progression (PD) or bleeding.
b. In the baseline period, through clinical examination and post-treatment brain imaging (computerized tomography [CT] scan or magnetic resonance imaging [MRI]), it is determined that there is no need to continue using dexamethasone.
c. Anticonvulsants are allowed, but the dosage must be maintained (stable) at least 2 weeks before the patient signs the informed consent.
d. The treatment of brain metastases can include whole brain radiation, radiosurgery (Gamma Knife®, linear particle accelerator or equivalent treatment), or a combination of treatments deemed appropriate by the attending physician. All treatments for brain metastases must be completed at least 14 days before day 0 of cycle 1.
11. Determine good organ function according to the following indicators:
a. Bone marrow reserve capacity:
i. The number of white blood cells >=3×103/microliter (μL);
ii. The absolute number of neutrophils (sections and bands) >= 1.5×103/μl (μL);
iii. The number of platelets >=100×103/microliter (μL);
iv. Hemoglobin >=9.0 grams per deciliter (g/dL), and there is no blood transfusion at least 2 weeks before the 0th day of the first cycle.
b. Liver:
i. Total bilirubin <=1.5 times the upper limit of normal (ULN); except for the short-term increase of indirect bilirubin caused by Gilbert's syndrome;
ii. Alkaline phosphoric acid enzyme, alanine transamination enzyme and/or aspartic acid transamination enzyme <= 3 times the upper limit of normal (ULN). If it is not related to liver metastasis, further evaluation should be made for the significant concentration of alanine transamine enzyme or aspartic acid transamine enzyme to confirm viral hepatitis. (Note: It is permissible for the individual concentration of alkaline phosphate enzyme to increase by more than 3 times the upper limit of normal (ULN) due to bone metastasis.)
c. Kidney:
i. Creatinine clearance rate (CrCl) calculated according to the original Cockcroft-Gault formula calculated by body weight (CrCl) >= 45 ml/min (mL/min);
ii. Urine protein (tested with test paper): 0 or 1+. Only if the protein collected in the 24-hour urine is <2g, it can be included in >= 2+ patients.
12. Reproductive patients and their partners must use contraceptive methods during the entire trial period and 6 months after the trial is interrupted.
a. Reproductive patients must be willing to use two high-efficiency double-barrier contraceptive methods for contraception, or abstain from sex during the trial period.
i. In particular, female patients with fertility must continue and correctly use methods that have a failure rate of less than 1% per year, such as implants, injections, comprehensive oral contraceptives, uterine contraceptives, abstinence, or their partners The vas deferens has been ligated.
ii. Reproductive male patients (defined as men who have not undergone vasectomy) must use condoms with spermicide, and their female partners must use another effective method of contraception.
Exclusion Criteria
Subject exclusion conditions
If you meet any of the following conditions, you will not be able to participate in this trial:
1. During pregnancy or breastfeeding.
2. There is a histology/cytology record confirmed as one of the following:
a. Squamous non-small cell lung cancer. (Note: If it is a mixed tumor histology/cytology or the main cell type is non-squamous cells, the qualification will be determined based on the main cell type must be non-squamous cells.)
b. Patients with neuroendocrine histology of any small cell type or large cell type.
3. Recently (within 6 months before the 0th day of the 1st cycle), a heart condition defined as grade II, III or IV according to the New York Heart Association has occurred.
4. Recent (within 6 months before day 0 of cycle 1) a history of major vascular events (such as aortic aneurysms that require surgical repair, or recent peripheral arterial blockage) and/or major and unstable blood vessels Medical history of the disease.
5. A history of stroke or transient ischemic attack within 6 months before the 0th day of cycle 1, or a long-term history of more than one of the following vascular embolism events:
a. Cerebrovascular accident
b. Temporary ischemic attack
c. Myocardial infarction
d. Vessel embolism reaction, including pulmonary embolism
6. Are receiving anticoagulant therapy for the following conditions:
a. It is not considered "stable", defined as the dose not being maintained for at least 3 months before the 0th day of the first cycle.
b. When signing the consent form, the International Normalized Ratio (INR) was not within the target range.
7. The central nervous system (CNS) has the latest diagnosis, medical history, or risk of bleeding, including the following:
a. Patients with CNS metastasis have undergone neurosurgical resection or brain biopsy within 8 weeks before the 0th day of cycle 1.
b. Patients should have stopped corticosteroids for at least 1 week (7 days) during computerized tomography (CT)/MRI (MRI) of the brain after treatment (applicable for CNS transfer).
8. Any previous history of hypertensive crisis and/or hypertensive encephalopathy, or currently diagnosed or recently under-controlled hypertension (defined as systolic blood pressure> 150 mmHg when taking antihypertensive drugs Column (mm Hg) and/or diastolic blood pressure> 100 millimeters of mercury (mm Hg)).
9. Have a recent history of any of the following:
a. Major surgery, traditional biopsy, open pleural adhesion surgery, or major traumatic injury occurred within 28 days before the 0th day of the first cycle.
b. Have a history of symptoms that may require surgery during the trial period or within 6 months before signing the subject's consent form.
c. Thick needle sections or other minor operations have been performed within 7 days before the 0th day of the 1st cycle. (Note: It is allowed to insert venous access devices or closed pleural adhesions, thoracentesis or mediastinoscopy.)
10. Have any of the following medical history:
a. Have coughed up blood (about> 2.5 ml or half a teaspoon) within 3 months before the 0th day of cycle 1.
b. There are tumors located in the thoracic cavity, center, and mediastinum within 2 cm of the carina, invading or adjacent to major blood vessels (according to the radiologist's assessment), and the risk of bleeding is judged by PI.
c. Cavitation of the lung tumor, if the diameter of the lesion exceeds 50%, and/or the central bronchi or blood vessels are involved.
-The main blood vessels are defined as:
• Aorta
• superior vena cava and inferior vena cava
• Main Pulmonary Artery
• Intrapericardial parts of the right and left pulmonary arteries and pulmonary veins
-The center position is defined as:
• The distance from the carina is less than or equal to 2 cm
The above criteria will be discussed with the radiologists, PIs and medical monitors of the experimental unit, and the exclusion condition item 10 will be evaluated according to individual circumstances.
11. There is a history of gastrointestinal (GI) 瘻 tubes, perforations or abscesses.
12. Currently diagnosed or have a history of unhealed wounds, active ulcers or untreated fractures.
13. Have a history of suffering from another malignant tumor in the past 5 years, but does not include successfully cured superficial basal cell carcinoma, superficial/cutaneous squamous cell carcinoma or carcinoma in situ.
14. Known to be allergic to carboplatin, paclitaxel, bevacizumab, Chinese hamster ovary cell preparations, or other human recombinant or humanized antibodies.
15. Before the 0th day of cycle 1, received any other experimental drug treatment within the past 30 days or 5 half-lives (if any; whichever is longer).
16. Have received the following treatment before:
a. Paclitaxel
b. Bevacizumab (Note: Having received intravitreal injection of bevacizumab will not be excluded from participation in this trial in advance.)
c. Anthracycline (Note: After consulting a medical monitor and determining that the risk of increased heart failure can be ruled out, it can be allowed according to the individual case.)
17. If the record shows or is known to have alcohol/drug abuse, the ability to comply with the test plan shall be excluded in advance.
18. Have any of the following combined treatments or conditions:
a. Combine vaccines containing weakened viruses, such as yellow fever vaccine.
b. Known history of active or latent tuberculosis.
c. There are concurrent systemic diseases (such as active infections, including known infections with human immunodeficiency virus, hepatitis B or C virus), and the test host (or his designee) believes that the safety of the patient will be endangered ( Such as potential drug interactions, or the ability to comply with test plan books).
d. Any other complication that may increase the risk of the patient and/or may affect the ability of the trial leader (or its designee) to manage the trial plan will be excluded from participation in this trial in advance.
If you meet any of the following conditions, you will not be able to participate in this trial:
1. During pregnancy or breastfeeding.
2. There is a histology/cytology record confirmed as one of the following:
a. Squamous non-small cell lung cancer. (Note: If it is a mixed tumor histology/cytology or the main cell type is non-squamous cells, the qualification will be determined based on the main cell type must be non-squamous cells.)
b. Patients with neuroendocrine histology of any small cell type or large cell type.
3. Recently (within 6 months before the 0th day of the 1st cycle), a heart condition defined as grade II, III or IV according to the New York Heart Association has occurred.
4. Recent (within 6 months before day 0 of cycle 1) a history of major vascular events (such as aortic aneurysms that require surgical repair, or recent peripheral arterial blockage) and/or major and unstable blood vessels Medical history of the disease.
5. A history of stroke or transient ischemic attack within 6 months before the 0th day of cycle 1, or a long-term history of more than one of the following vascular embolism events:
a. Cerebrovascular accident
b. Temporary ischemic attack
c. Myocardial infarction
d. Vessel embolism reaction, including pulmonary embolism
6. Are receiving anticoagulant therapy for the following conditions:
a. It is not considered "stable", defined as the dose not being maintained for at least 3 months before the 0th day of the first cycle.
b. When signing the consent form, the International Normalized Ratio (INR) was not within the target range.
7. The central nervous system (CNS) has the latest diagnosis, medical history, or risk of bleeding, including the following:
a. Patients with CNS metastasis have undergone neurosurgical resection or brain biopsy within 8 weeks before the 0th day of cycle 1.
b. Patients should have stopped corticosteroids for at least 1 week (7 days) during computerized tomography (CT)/MRI (MRI) of the brain after treatment (applicable for CNS transfer).
8. Any previous history of hypertensive crisis and/or hypertensive encephalopathy, or currently diagnosed or recently under-controlled hypertension (defined as systolic blood pressure> 150 mmHg when taking antihypertensive drugs Column (mm Hg) and/or diastolic blood pressure> 100 millimeters of mercury (mm Hg)).
9. Have a recent history of any of the following:
a. Major surgery, traditional biopsy, open pleural adhesion surgery, or major traumatic injury occurred within 28 days before the 0th day of the first cycle.
b. Have a history of symptoms that may require surgery during the trial period or within 6 months before signing the subject's consent form.
c. Thick needle sections or other minor operations have been performed within 7 days before the 0th day of the 1st cycle. (Note: It is allowed to insert venous access devices or closed pleural adhesions, thoracentesis or mediastinoscopy.)
10. Have any of the following medical history:
a. Have coughed up blood (about> 2.5 ml or half a teaspoon) within 3 months before the 0th day of cycle 1.
b. There are tumors located in the thoracic cavity, center, and mediastinum within 2 cm of the carina, invading or adjacent to major blood vessels (according to the radiologist's assessment), and the risk of bleeding is judged by PI.
c. Cavitation of the lung tumor, if the diameter of the lesion exceeds 50%, and/or the central bronchi or blood vessels are involved.
-The main blood vessels are defined as:
• Aorta
• superior vena cava and inferior vena cava
• Main Pulmonary Artery
• Intrapericardial parts of the right and left pulmonary arteries and pulmonary veins
-The center position is defined as:
• The distance from the carina is less than or equal to 2 cm
The above criteria will be discussed with the radiologists, PIs and medical monitors of the experimental unit, and the exclusion condition item 10 will be evaluated according to individual circumstances.
11. There is a history of gastrointestinal (GI) 瘻 tubes, perforations or abscesses.
12. Currently diagnosed or have a history of unhealed wounds, active ulcers or untreated fractures.
13. Have a history of suffering from another malignant tumor in the past 5 years, but does not include successfully cured superficial basal cell carcinoma, superficial/cutaneous squamous cell carcinoma or carcinoma in situ.
14. Known to be allergic to carboplatin, paclitaxel, bevacizumab, Chinese hamster ovary cell preparations, or other human recombinant or humanized antibodies.
15. Before the 0th day of cycle 1, received any other experimental drug treatment within the past 30 days or 5 half-lives (if any; whichever is longer).
16. Have received the following treatment before:
a. Paclitaxel
b. Bevacizumab (Note: Having received intravitreal injection of bevacizumab will not be excluded from participation in this trial in advance.)
c. Anthracycline (Note: After consulting a medical monitor and determining that the risk of increased heart failure can be ruled out, it can be allowed according to the individual case.)
17. If the record shows or is known to have alcohol/drug abuse, the ability to comply with the test plan shall be excluded in advance.
18. Have any of the following combined treatments or conditions:
a. Combine vaccines containing weakened viruses, such as yellow fever vaccine.
b. Known history of active or latent tuberculosis.
c. There are concurrent systemic diseases (such as active infections, including known infections with human immunodeficiency virus, hepatitis B or C virus), and the test host (or his designee) believes that the safety of the patient will be endangered ( Such as potential drug interactions, or the ability to comply with test plan books).
d. Any other complication that may increase the risk of the patient and/or may affect the ability of the trial leader (or its designee) to manage the trial plan will be excluded from participation in this trial in advance.
The Estimated Number of Participants
-
Taiwan
24 participants
-
Global
478 participants
