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

Phase 2

Recruiting

• Conditions: Advanced Esophageal Squamous Cell Carcinoma
• Interventions: Drug: Afatinib; Drug: Irinotecan

• Registration Number: NCT05818982
• Lead Sponsor: Peking University

Brief Summary

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

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.

Study Timeline

• Study Start: 2023-02-09
• Status Verified: 2023-04
• Study First Submitted: 2023-04-06
• Study First Submitted QC: 2023-04-06
• Last Update Submitted: 2023-04-06
• Study First Posted: 2023-04-19
• Last Update Posted: 2023-04-19
• Primary Completion: 2025-02
• Study Completion: 2026-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

1. Agree to participate and sign the informed consent form in writing;
2. Age: 18-75 years old;
3. No gender limit;
4. Esophageal squamous cell carcinoma diagnosed by pathology;
5. The results of 3-gene RNA sequencing (ALTRK) in tumor tissue were negative;
6. Imagingly confirmed unresectable advanced esophageal squamous cell carcinoma;
7. Failure of previous platinum-containing regimens and immunotherapy regimens (PD-1/PD-L1 monoclonal antibody);
8. 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;
9. Estimated survival≥ 3 months;
10. General Physical Condition (ECOG) 0-1;
11. 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

1. Those who are currently receiving other effective programs;
2. Patients who have participated in other clinical trials within 4 weeks before enrollment;
3. There is no measurable tumor foci, such as fluid accumulation in the body cavity or diffuse infiltration of organs;
4. Those who have received radiotherapy for measurable lesions;
5. Previous anti-EGFR monoclonal antibody or EGFR-TKI treatment;
6. 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;
7. 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;
8. Neurological or psychiatric abnormalities affecting cognitive ability, including central nervous system metastases;
9. Active severe clinical infection (grade >2 NCI-CTCAE version 5.0) within 14 days prior to enrollment, including active TB;
10. Known or reported HIV infection or active hepatitis B or C;
11. Uncontrolled systemic diseases, such as poorly controlled diabetes;
12. History of interstitial lung disease, such as interstitial pneumonia, pulmonary fibrosis, or evidence of interstitial lung disease on baseline chest x-ray/CT;
13. Keratitis, ulcerative keratitis or severe dry eye;
14. Known hypersensitivity or anaphylaxis to any component of the investigational drug;
15. Pregnancy (determined by serum β-chorionic gonadotropin test) or breastfeeding;
16. 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;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort A	Afatinib	Group A received afatinib (40 mg oral/day) every 6 weeks
Cohort B	Irinotecan	Group B received irinotecan (140-180mg/m2 intravenous) every 2 weeks

Primary Outcome Measures

Name	Time	Method
Progression-free survival	2 years	PFS is defined as the time from the first dose to the date of the disease progression or death from any cause.

Secondary Outcome Measures

Name	Time	Method
Objective response rate	2 years	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.
Disease control rate	2 years	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.
Overall survival	2 years	OS is defined as the time from the first dose to the date of death due to any cause.
Adverse Events	2 years	Incidence and severity of adverse events.

Trial Locations

Locations (3)

Xinxiang Central Hospital of Henan Province, Xinxiang, China; 🇨🇳 Xinxiang, China

Beijing Cancer Hospital, Beijing, China; 🇨🇳 Beijing, China

First Hospital of Xiamen University Affiliated Hospital,Xiamen,China; 🇨🇳 Xiamen, China