Molecular Characterization and Clinical Outcomes of ALK Tyrosine Kinase Inhibitors in ALK-rearranged Advanced Squamous Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Crizotinib
- Conditions
- Non-small Cell Lung Cancer
- Sponsor
- Hunan Province Tumor Hospital
- Enrollment
- 120
- Locations
- 1
- Primary Endpoint
- Progression-free survival (PFS)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This study was to explore the efficacy of ALK-TKI in lung squamous cell carcinoma. Approximately 5% of lung adenocarcinomas have oncogenic fusions of EML-4 and ALK a mutation associated with tumorigenesis and migration.
Detailed Description
This research focuses on exploring epidemiology, distributions and the efficacy and prognosis of ALK-TKI in lung squamous cell carcinoma.Approximately 5% of lung adenocarcinomas have oncogenic fusions of EML-4 and ALK a mutation associated with tumorigenesis and migration. Several studies have shown that in patients with ALK-rearranged non-small cells, the use of ALK inhibitors can achieve better efficacy and significantly prolong overall survival. However few of them performed Fish or NGS tests. Our data demonstrates that lung squamous cell carcinoma with ALK rearrangement responds well to ALK-TKI, and correspondingly has a significant improvement in survival time and prognosis, providing a basis for the treatment of ALK-positive patients with lung squamous cell carcinoma. At the same time, we believe that genetic testing is also required for lung squamous cell carcinoma to achieve more accurate medication.
Investigators
Yongchang Zhang
Professor, Director of Clinical Trial Center
Hunan Province Tumor Hospital
Eligibility Criteria
Inclusion Criteria
- •Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.
- •Age ≥ 18 years.
- •Histopathology or cytology confirmed and recorded local progression or metastatic Advanced Squamous Cell Carcinoma without systemic treatment.
- •ALK fusion positive evaluated by IHC (ventana), NGS or FISH.
- •Predicted survival ≥ 12 weeks.
- •Adequate bone marrow hematopoiesis and organ function
- •Presence of measurable lesions according to RECIST 1.
- •Subjects with stable brain metastases may be included in the study.
Exclusion Criteria
- •Prior systemic therapy for locally advanced or metastatic disease.
- •Subjects who have received any of the following treatments must be excluded:
- •Treatment with molecules such as EGFR, VEGFR antibodies within 4 weeks prior to the first dose of study drug.
- •Have received radiation within 14 days prior to the first dose or have not recovered from radiation-related toxicity. Chest and extra-brain palliative radiotherapy, stereotactic radiosurgery, and stereotactic body radiotherapy may be performed 7 days prior to the first dose.
- •Ongoing (or inability to discontinue) possibly potent CYP1A2, CYP3A inhibitor (1 week), or inducer (2 weeks) drug therapy or herbal supplements within 1-2 weeks prior to the first dose.
- •Presence of spinal cord compression or meningeal metastasis.
- •History of other malignant tumors within 2 years.
- •Adverse events (except alopecia of any degree) of CTCAE \> grade 1 due to prior treatment (e.g., adjuvant chemotherapy, radiotherapy, etc.) prior to the first dose.
- •History of stroke or intracranial hemorrhage within 6 months prior to the first dose.
- •The presence of any severe or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding in the judgment of the investigator.
Arms & Interventions
Cohort A, first line ALK-TKIs
All the patients were treated with first line ALK-TKis including Crizotinib, Alectinib, Brigatinib and Lorlatinib etc. Approximately 30 patients.
Intervention: Crizotinib
Cohort B, second line ALK-TKIs
All the patients were treated with second line ALK-TKis including Crizotinib, Alectinib, Brigatinib and Lorlatinib etc. Approximately 30 patients.
Intervention: Crizotinib
Cohort C, post second line ALK-TKIs
All the patients were treated with post second ALK-TKis including Crizotinib, Alectinib, Brigatinib and Lorlatinib etc. Approximately 30 patients.
Intervention: Crizotinib
Outcomes
Primary Outcomes
Progression-free survival (PFS)
Time Frame: Time from first subject dose to study completion, or up to 36 month
To assess progression-free survival of patients treated by different treatment according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator, define as first dose to first documented disease progression assessed by investigator or death due to any cause
Secondary Outcomes
- Objective Response Rate (ORR)(Time from first dose to last dose, or up to 24 month.)
- Overall survival (OS)(Time from first subject dose to study completion, or up to 36 month.)