X-396(Ensartinib) Capsules in ALK-Positive NSCLC Patients With Brain Metastases
Study Details
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: X-396(Ensartinib) Capsule
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Drug: X-396(Ensartinib) Capsule
All consented, enrolled, eligible patients receive X-396 capsules, 225mg once daily.
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Outcome Measures
Primary Outcome Measures
- Intracranial objective response rate (iORR) based on investigator assessment according to RNAO-BM. [12 weeks]
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. [12 weeks]
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 [36 months]
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. [36 months]
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. [36 months]
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 [12 weeks]
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 [12 weeks]
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 [36 months]
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 [36 months]
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 [36 months]
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. [12 weeks]
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 [12 weeks]
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 [36 months]
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 [36 months]
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 [36 months]
Defined as time from documentation of overall response (CR or PR) to overall disease progression or death, assessed by investigator.
- Overall survival (OS) [36 months]
Defined as time from first dose of X-396 to death due to any causes.
- Incidence of patients experiencing adverse events. [36 months]
Incidence of adverse events occurred during the study (from the timeoint of signing a informed consent form to 30days after the end of trial).
Eligibility Criteria
Criteria
Inclusion Criteria:
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- Histologically or cytologically confirmed locally advance or recurrent/metastatic NSCLC that was positive for ALK mutations.
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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.
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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.
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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 ≥1.510^9/L,platelets count ≥8010^9/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.
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Drug related toxicities has been relieved to grade 1 (based on NCI CTCAE v4.03), except for hair loss.
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Being willing and able to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
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Signed and dated informed consent.
Exclusion Criteria:
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- 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.
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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.
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Patients who previously received organ transplantation or stem cell transplantation.
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Patients with clinically significant cardiovascular and cerebrovascular diseases.
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Patients with dysphagia, active gastrointestinal diseases or other conditions that will interfere significantly with the absorption, distribution, metabolism or excretion of study medication.
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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.
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Patients with interstitial lung disease history or signs of active interstitial lung disease.
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Pregnant and lactating women. 11. Patients with known allergy or delayed hypersensitivity reaction to study drug or its excipients.
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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.
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Patients who are currently under treatment of warfarin or other coumarin anticoagulants.
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Patients with other illness or medical conditions potentially interfering with the study treatment.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Fudan University
- Betta Pharmaceuticals Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BTP-42324-IIT