To Evaluate the Efficacy and Safety of Afatinib for Advanced ALTRK-negative ESCC

Study Overview
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Brief Summary
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This is a phase II study to evaluate the effectiveness and safety of Afininib compared to irinotecan in the 3-gene RNA sequencing (ALTRK) negative advanced esophageal squamous squamous carcinoma.

Detailed Description
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Participants were assigned to either group A or group B at 2:1 randomization (block randomization). Group A received afatinib (40 mg orally/day) every 6 weeks; Group B received irinotecan (140-180mg/m2 intravenous) every 2 weeks.

Official Title
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A Multicenter, Open-label, Randomized, Controlled Phase II Study to Evaluate the Efficacy and Safety of Afatinib Versus Irinotecan as a Second-line and Above Treatment for Advanced ALTRK-negative ESCC

Conditions
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Advanced Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Afatinib
* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Agree to participate and sign the informed consent form in writing; Age: 18-75 years old; No gender limit; Esophageal squamous cell carcinoma diagnosed by pathology; The results of 3-gene RNA sequencing (ALTRK) in tumor tissue were negative; Imagingly confirmed unresectable advanced esophageal squamous cell carcinoma; Failure of previous platinum-containing regimens and immunotherapy regimens (PD-1/PD-L1 monoclonal antibody); At least one measurable lesion (according to RECIST1.1 criteria) or non-measurable lesion that can be evaluated, with imaging diagnosis ≤ 21 days from enrollment; Estimated survival≥ 3 months; General Physical Condition (ECOG) 0-1; Sufficient bone marrow hematopoietic function (within 7 days): hemoglobin ≥ 9 g/dL, white blood cell ≥ 3.0×10^9/L, neutrophil ≥1.5×10^9/L, platelet ≥ 100×10^9/L; Normal liver and kidney function (within 14 days): TBIL ≤ 1.5 times the upper limit of normal; ALT and AST ≤ 2.5 times the upper limit of normal, and if liver metastases are present, ≤ 5 times the upper limit of normal; Creatinine ≤ 1.5 times the upper limit of normal; Exclusion Criteria: Those who are currently receiving other effective programs; Patients who have participated in other clinical trials within 4 weeks before enrollment; There is no measurable tumor foci, such as fluid accumulation in the body cavity or diffuse infiltration of organs; Those who have received radiotherapy for measurable lesions; Previous anti-EGFR monoclonal antibody or EGFR-TKI treatment; Patients with other primary malignant tumors other than esophageal cancer at the same time, except for cured skin basal cell carcinoma and cervical carcinoma in situ; Clinically significant cardiovascular diseases, such as heart failure (NYHA GRADE III-IV), uncontrolled coronary heart disease, cardiomyopathy, arrhythmia, uncontrolled hypertension or history of myocardial infarction within the past 1 year; Neurological or psychiatric abnormalities affecting cognitive ability, including central nervous system metastases; Active severe clinical infection (grade >2 NCI-CTCAE version 5.0) within 14 days prior to enrollment, including active TB; Known or reported HIV infection or active hepatitis B or C; Uncontrolled systemic diseases, such as poorly controlled diabetes; History of interstitial lung disease, such as interstitial pneumonia, pulmonary fibrosis, or evidence of interstitial lung disease on baseline chest x-ray/CT; Keratitis, ulcerative keratitis or severe dry eye; Known hypersensitivity or anaphylaxis to any component of the investigational drug; Pregnancy (determined by serum β-chorionic gonadotropin test) or breastfeeding; The investigator determines that there are abnormal heart or lung or kidney or liver function that is not suitable for the treatment of this study;

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>Group A received afatinib (40 mg oral/day) every 6 weeks | Drug: Afatinib<br>* Afatinib will be administered orally at 40 mg per day (qd) in each 6-week cycle.<br>|
| Active Comparator: Cohort B<br>Group B received irinotecan (140-180mg/m2 intravenous) every 2 weeks | Drug: Irinotecan<br>* Irinotecan, intravenous drip, 140-180mg/㎡, D1, Q14D<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | PFS is defined as the time from the first dose to the date of the disease progression or death from any cause. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | The Objective Response Rate (ORR) is the percentage of participants who achieved Complete Response (CR) or Partial Response (PR) based on RECIST version 1.1. | 2 years | 
| Disease control rate | Disease control rate (DCR) is the percentage of participants who achieved Complete Response (CR) or Partial Response (PR) or Stable disease (SD) based on RECIST version 1.1. | 2 years | 
| Overall survival | OS is defined as the time from the first dose to the date of death due to any cause. | 2 years | 
| Adverse Events | Incidence and severity of adverse events. | 2 years |