Back to resultsX-396(Ensartinib) Capsules in ALK-Positive NSCLC Patients With Brain Metastases
Primary Purpose
Nonsmall Cell Lung Cancer, Brain Metastases
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
X-396(Ensartinib) Capsule
Sponsored by
About this trial
This is an interventional treatment trial for Nonsmall Cell Lung Cancer focused on measuring NSCLC, Brain metastases, ALK mutations, X-396 (Ensartinib)
Eligibility Criteria
Inclusion Criteria:
1. Histologically or cytologically confirmed locally advance or recurrent/metastatic NSCLC that was positive for ALK mutations.
2. Contrast-enhanced MRI or CT confirmed parenchymal brain metastases with at least one measurable lesion (according to RANO and RECIST 1.1), which was not previously treated with radiotherapy.
3. At most once treated with chemotherapy, which must have been completed at least 4 weeks before the initiation of study treatment. Any adverse events related to previous chemotherapy treatment have disappeared.
4. Female or male, 18 years of age or older 5. A Karnofsky Performance Status score of at least 60. 6. An expected survival time of at least 12 weeks. 7. Adequate organ functions, defined as absolute neutrophils count ≥1.5*10^9/L，platelets count ≥80*10^9/L, hemoglobin concentration≥ 9 g/dL, total bilirubin ≤1.5 *ULN (upper limits of normal), ALT≤2.5 *ULN, AST≤2.5 *ULN, creatinine≤1.5 *ULN.
8. Drug related toxicities has been relieved to grade 1 (based on NCI CTCAE v4.03), except for hair loss.
9. Being willing and able to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
10. Signed and dated informed consent.
Exclusion Criteria:
1. Currently under treatment of other systemic anti-cancer therapies. 2. Evidence of active malignancy within last 5 years. 3. Patients who participated in other clinical trials within last 4 weeks before the initiation of study treatment.
4. Patients who received surgery or immunotherapy within last 4 weeks before the initiation of study treatment, or received radiotherapy within last 2 weeks before the initiation of study treatment.
5. Patients who previously received organ transplantation or stem cell transplantation.
6. Patients with clinically significant cardiovascular and cerebrovascular diseases.
7. Patients with dysphagia, active gastrointestinal diseases or other conditions that will interfere significantly with the absorption, distribution, metabolism or excretion of study medication.
8. Patients who are active carrier of hepatitis B (HBsAg positive and HBV-DNA ≥500IU/mL), hepatitis C virus antibody, treponema pallidum antibody or HIV antibody.
9. Patients with interstitial lung disease history or signs of active interstitial lung disease.
10. Pregnant and lactating women. 11. Patients with known allergy or delayed hypersensitivity reaction to study drug or its excipients.
12. Patients who need to receive drugs which could induce QT/QTc interval prolongation or torsade de pointes, or drugs which are potent CYP3A4 inhibitors or inducers within last 14 days before the initiation of study treatment and during the study.
13. Patients who are currently under treatment of warfarin or other coumarin anticoagulants.
14. Patients with other illness or medical conditions potentially interfering with the study treatment.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
X-396(Ensartinib) Capsule
Arm Description
Outcomes
Primary Outcome Measures
Intracranial objective response rate (iORR) based on investigator assessment according to RNAO-BM.
iORR per RANO-BM calculated as the proportion of patients with a best intracranial overall response defined as complete response (CR) or partial response (PR), based on investigator assessment.
Secondary Outcome Measures
Disease control rate based on intracranial response (iDCR) according to RANO-BM.
Defined as the percentage of patients who have achieved intracranial overall response of CR, PR and stable disease (SD), assessed by investigator.
Progression-free survival based on intracranial response (iPFS) according to RANO-BM
Defined as time from first dose of X-396 capsule to intracranial disease progression or death due to any causes, assessed by investigator.
Time to progression based on intracranial response (iTTP) according to RANO-BM.
Defined as time from first dose of X-396 capsule to intracranial disease progression, assessed by investigator.
Duration of response based on intracranial response (iDOR) according to RANO-BM.
Defined as time from documentation of intracranial response (CR or PR) to intracranial disease progression or death, assessed by investigator.
Intracranial objective response rate (iORR) based on intracranial response according to RECIST 1.1
iORR per RECIST 1.1 calculated as the proportion of patients with a best intracranial overall response defined as complete response (CR) or partial response (PR), based on investigator assessment.
Disease control rate based on intracranial response (iDCR) according to RECIST 1.1
Defined as the percentage of patients who have achieved intracranial overall response of CR, PR and stable disease (SD), assessed by investigator.
Progression-free survival based on intracranial response (iPFS) according to RECIST 1.1
Defined as time from first dose of X-396 capsule to intracranial disease progression or death due to any causes, assessed by investigator.
Time to progression based on intracranial response (iTTP) according to RECIST 1.1
Defined as time from first dose of X-396 capsule to intracranial disease progression, assessed by investigator.
Duration of response based on intracranial response (iDOR) according to RECIST 1.1
Defined as time from documentation of intracranial response (CR or PR) to intracranial disease progression or death, assessed by investigator.
Objective response rate (ORR) based on overall response according to RECIST 1.1.
ORR per RECIST 1.1 calculated as the proportion of patients with a best overall response defined as complete response (CR) or partial response (PR), based on investigator assessment.
Disease control rate based on overall response (DCR) according to RECIST 1.1
Defined as the percentage of patients who have achieved overall response of CR, PR and stable disease (SD), assessed by investigator.
Progression-free survival based on overall response (PFS) according to RECIST 1.1
Defined as time from first dose of X-396 capsule to overall disease progression or death due to any causes, assessed by investigator.
Time to progression based on overall response (TTP) according to RECIST 1.1
Defined as time from first dose of X-396 capsule to overall disease progression, assessed by investigator.
Duration of response based on overall response (DOR) according to RECIST 1.1
Defined as time from documentation of overall response (CR or PR) to overall disease progression or death, assessed by investigator.
Overall survival (OS)
Defined as time from first dose of X-396 to death due to any causes.
Incidence of patients experiencing adverse events.
Incidence of adverse events occurred during the study (from the timeoint of signing a informed consent form to 30days after the end of trial).
Full Information
NCT ID
NCT03753685
First Posted
November 22, 2018
Last Updated
November 22, 2018
Sponsor
Fudan University
Collaborators
Betta Pharmaceuticals Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT03753685
Brief Title
X-396(Ensartinib) Capsules in ALK-Positive NSCLC Patients With Brain Metastases
Official Title
Efficacy and Safety of X-396(Ensartinib) in ALK-Positive NSCLC Patients With Brain Metastases: A Phase Ⅱ, Open-Label, Single Arm, Multicenter Study
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Unknown status
Study Start Date
December 2018 (Anticipated)
Primary Completion Date
July 2020 (Anticipated)
Study Completion Date
October 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University
Collaborators
Betta Pharmaceuticals Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
To assess efficacy and safety of oral X-396 (Ensartinib) capsule in Chinese ALK-positive NSCLC patients with brain metastases, eligible patients will be enrolled with objective responses being primary outcome measures.
Detailed Description
In this phase Ⅱ, open-label, single arm, multicenter study, efficacy and safety of oral X-396 capsule (Ensartinib) in 37 Chinese ALK-positive NSCLC patients with brain metastases will be assessed. Eligible patients will receive 225mg X-396 capsules once daily and objective responses of brain metastasis based on investigator assessment according to Response Assessment in Neuro-Oncology (RANO) are primary outcome measures.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nonsmall Cell Lung Cancer, Brain Metastases
Keywords
NSCLC, Brain metastases, ALK mutations, X-396 (Ensartinib)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
X-396(Ensartinib) Capsule
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
X-396(Ensartinib) Capsule
Intervention Description
All consented, enrolled, eligible patients receive X-396 capsules, 225mg once daily.
Primary Outcome Measure Information:
Title
Intracranial objective response rate (iORR) based on investigator assessment according to RNAO-BM.
Description
iORR per RANO-BM calculated as the proportion of patients with a best intracranial overall response defined as complete response (CR) or partial response (PR), based on investigator assessment.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Disease control rate based on intracranial response (iDCR) according to RANO-BM.
Description
Defined as the percentage of patients who have achieved intracranial overall response of CR, PR and stable disease (SD), assessed by investigator.
Time Frame
12 weeks
Title
Progression-free survival based on intracranial response (iPFS) according to RANO-BM
Description
Defined as time from first dose of X-396 capsule to intracranial disease progression or death due to any causes, assessed by investigator.
Time Frame
36 months
Title
Time to progression based on intracranial response (iTTP) according to RANO-BM.
Description
Defined as time from first dose of X-396 capsule to intracranial disease progression, assessed by investigator.
Time Frame
36 months
Title
Duration of response based on intracranial response (iDOR) according to RANO-BM.
Description
Defined as time from documentation of intracranial response (CR or PR) to intracranial disease progression or death, assessed by investigator.
Time Frame
36 months
Title
Intracranial objective response rate (iORR) based on intracranial response according to RECIST 1.1
Description
iORR per RECIST 1.1 calculated as the proportion of patients with a best intracranial overall response defined as complete response (CR) or partial response (PR), based on investigator assessment.
Time Frame
12 weeks
Title
Disease control rate based on intracranial response (iDCR) according to RECIST 1.1
Description
Defined as the percentage of patients who have achieved intracranial overall response of CR, PR and stable disease (SD), assessed by investigator.
Time Frame
12 weeks
Title
Progression-free survival based on intracranial response (iPFS) according to RECIST 1.1
Description
Defined as time from first dose of X-396 capsule to intracranial disease progression or death due to any causes, assessed by investigator.
Time Frame
36 months
Title
Time to progression based on intracranial response (iTTP) according to RECIST 1.1
Description
Defined as time from first dose of X-396 capsule to intracranial disease progression, assessed by investigator.
Time Frame
36 months
Title
Duration of response based on intracranial response (iDOR) according to RECIST 1.1
Description
Defined as time from documentation of intracranial response (CR or PR) to intracranial disease progression or death, assessed by investigator.
Time Frame
36 months
Title
Objective response rate (ORR) based on overall response according to RECIST 1.1.
Description
ORR per RECIST 1.1 calculated as the proportion of patients with a best overall response defined as complete response (CR) or partial response (PR), based on investigator assessment.
Time Frame
12 weeks
Title
Disease control rate based on overall response (DCR) according to RECIST 1.1
Description
Defined as the percentage of patients who have achieved overall response of CR, PR and stable disease (SD), assessed by investigator.
Time Frame
12 weeks
Title
Progression-free survival based on overall response (PFS) according to RECIST 1.1
Description
Defined as time from first dose of X-396 capsule to overall disease progression or death due to any causes, assessed by investigator.
Time Frame
36 months
Title
Time to progression based on overall response (TTP) according to RECIST 1.1
Description
Defined as time from first dose of X-396 capsule to overall disease progression, assessed by investigator.
Time Frame
36 months
Title
Duration of response based on overall response (DOR) according to RECIST 1.1
Description
Defined as time from documentation of overall response (CR or PR) to overall disease progression or death, assessed by investigator.
Time Frame
36 months
Title
Overall survival (OS)
Description
Defined as time from first dose of X-396 to death due to any causes.
Time Frame
36 months
Title
Incidence of patients experiencing adverse events.
Description
Incidence of adverse events occurred during the study (from the timeoint of signing a informed consent form to 30days after the end of trial).
Time Frame
36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
1. Histologically or cytologically confirmed locally advance or recurrent/metastatic NSCLC that was positive for ALK mutations.
2. Contrast-enhanced MRI or CT confirmed parenchymal brain metastases with at least one measurable lesion (according to RANO and RECIST 1.1), which was not previously treated with radiotherapy.
3. At most once treated with chemotherapy, which must have been completed at least 4 weeks before the initiation of study treatment. Any adverse events related to previous chemotherapy treatment have disappeared.
4. Female or male, 18 years of age or older 5. A Karnofsky Performance Status score of at least 60. 6. An expected survival time of at least 12 weeks. 7. Adequate organ functions, defined as absolute neutrophils count ≥1.5*10^9/L，platelets count ≥80*10^9/L, hemoglobin concentration≥ 9 g/dL, total bilirubin ≤1.5 *ULN (upper limits of normal), ALT≤2.5 *ULN, AST≤2.5 *ULN, creatinine≤1.5 *ULN.
8. Drug related toxicities has been relieved to grade 1 (based on NCI CTCAE v4.03), except for hair loss.
9. Being willing and able to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
10. Signed and dated informed consent.
Exclusion Criteria:
1. Currently under treatment of other systemic anti-cancer therapies. 2. Evidence of active malignancy within last 5 years. 3. Patients who participated in other clinical trials within last 4 weeks before the initiation of study treatment.
4. Patients who received surgery or immunotherapy within last 4 weeks before the initiation of study treatment, or received radiotherapy within last 2 weeks before the initiation of study treatment.
5. Patients who previously received organ transplantation or stem cell transplantation.
6. Patients with clinically significant cardiovascular and cerebrovascular diseases.
7. Patients with dysphagia, active gastrointestinal diseases or other conditions that will interfere significantly with the absorption, distribution, metabolism or excretion of study medication.
8. Patients who are active carrier of hepatitis B (HBsAg positive and HBV-DNA ≥500IU/mL), hepatitis C virus antibody, treponema pallidum antibody or HIV antibody.
9. Patients with interstitial lung disease history or signs of active interstitial lung disease.
10. Pregnant and lactating women. 11. Patients with known allergy or delayed hypersensitivity reaction to study drug or its excipients.
12. Patients who need to receive drugs which could induce QT/QTc interval prolongation or torsade de pointes, or drugs which are potent CYP3A4 inhibitors or inducers within last 14 days before the initiation of study treatment and during the study.
13. Patients who are currently under treatment of warfarin or other coumarin anticoagulants.
14. Patients with other illness or medical conditions potentially interfering with the study treatment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jue Feng
Phone
021-64175590-88900
Email
13788956275@163.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
X-396(Ensartinib) Capsules in ALK-Positive NSCLC Patients With Brain Metastases
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