Alflutinib Versus Alflutinib Plus Chemotherapy for NSCLC

Study Overview
=================
Brief Summary
-----------------
Aim: the aim of this study is to investigated whether the combination of alflutinib with cytotoxic chemotherapy might hold additive efficacy, as well as tolerability .

Detailed Description
-----------------
alflutinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is active in the central nervous system (CNS) and which potently and selectively inhibits mutant forms of EGFR with both TKI-sensitising (activating) mutations and the T790M resistance-conferring mutation. However, resistance to alflutinib inevitably emerges. One promising strategy to further improve patient prognosis and to approach a cure is combination therapy with alflutinib and other agents such as cytotoxic chemotherapeutic drugs.

Official Title
-----------------
Alflutinib Versus Alflutinib Plus Chemotherapy for Nonesmall Cell Lung Cancer With EGFR (T790M)- Associated Resistance to Initial EGFR Inhibitor Treatment: An Open-label, Randomised Phase 2 Clinical Trial

Conditions
-----------------
NSCLC

Intervention / Treatment
-----------------
* Drug: Chemotherapy
* Drug: Alflutinib plus chemotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: histologically or cytologically diagnosed non-squamous NSCLC of stage IIIB or IV (based on the 7th edition of the TNM classification) or recurrent; an EGFR mutation, including an exon-19 deletion (Ex19del), L858R, or other (L861Q, G719A, G719C, or G719S), as well as the T790M mutation of EGFR as detected in a tissue or liquid biopsy sample obtained after disease progression during first-line EGFR-TKI (gefitinib, erlotinib, or afatinib) treatment; WHO performance status of 0 or 1; no prior neoadjuvant or adjuvant chemotherapy in the 12 months preceding study enrollment; adequate bone marrow reserve and organ function. Exclusion Criteria: treatment with an EGFR-TKI within 7 days of the first dose of the study treatment; symptomatic CNS metastases; evidence of interstitial pneumonia, pulmonary fibrosis, or radiation pneumonitis requiring steroid treatment as revealed by a computed tomography (CT) scan.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alflutinib plus chemotherapy<br>Those in the combination group received concurrent alflutinib (80 mg daily), as well as carboplatin (area under the curve [AUC] of 5 on day 1) and pemetrexed (500 mg/m2 on day 1) in a 3-week cycle for up to four cycles, followed by maintenance on alflutinib and pemetrexed until disease progression, unacceptable toxicity, or death. | Drug: Alflutinib plus chemotherapy<br>* Those in the combination group received concurrent alflutinib (80 mg daily), as well as carboplatin (area under the curve [AUC] of 5 on day 1) and pemetrexed (500 mg/m2 on day 1) in a 3-week cycle for up to four cycles, followed by maintenance on alflutinib and pemetrexed until disease progression, unacceptable toxicity, or death.<br>* Other names: Pulaile;|
| Sham Comparator: chemotherapy<br>arboplatin (area under the curve [AUC] of 5 on day 1) and pemetrexed (500 mg/m2 on day 1) in a 3-week cycle for up to four cycles, followed by maintenance on alflutinib and pemetrexed until disease progression, unacceptable toxicity, or death. | Drug: Chemotherapy<br>* Patients in the alflutinib group received alflutinib (80 mg daily) until disease progression, unacceptable toxicity, or death.<br>* Other names: Pulaile;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Disease-free survival | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective remission rate (ORR) | Objective remission rate | 16 weeks | 
| Disease Control Rate ( DCR) | Disease Control Rate | 16 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NSCLC ，EGFR(T790M)，alflutinib