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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Afatinib; Drug: Irinotecan

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 Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lin Shen, MD; Phone Number: +86-10-88196561; Email: linshenpku@163.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Cancer Hospital, Beijing, China
  • Xiamen, China
    • Not yet recruiting
    • First Hospital of Xiamen University Affiliated Hospital,Xiamen,China
    • Contact: Jiayi Li
  • Xinxiang, China
    • Not yet recruiting
    • Xinxiang Central Hospital of Henan Province, Xinxiang, China
    • Contact: Yinghua Ji

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking University

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2023
• Primary Completion (Anticipated): February 1, 2025
• Study Completion (Anticipated): February 1, 2026

Study Registration Dates

• First Submitted: April 6, 2023
• First Submitted That Met QC Criteria: April 6, 2023
• First Posted (Actual): April 19, 2023

Study Record Updates

• Last Update Posted (Actual): April 19, 2023
• Last Update Submitted That Met QC Criteria: April 6, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Protein Kinase Inhibitors; Topoisomerase I Inhibitors; Irinotecan; Afatinib
• Other Study ID Numbers: ESCC-ALTRK

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No