Study of Larotinib in Unresectable Advanced or Recurrent Esophageal Cancer

NCT04415853 | Recruiting Phase 3 DMC

• 1 other identifier: PCD-DZ650-20-001
• Study Type: interventional
• Target: 416
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, controlled, multi-center, open trial, unresectable locally advanced or metastatic esophageal squamous cell carcinoma patients that failed at least second-line treatment and overexpressed EGFR were enrolled and randomly assigned to the experimental group and control group at a 1: 1 ratio.,who received Larotinib and the chemotherapy regimen chosen by the investigator (Irinotecan Hydrochloride Injection or Tegafur Gimeracil Oteracil Potassium Capsule),respecitively. Subjects are administered until disease progression assessed by the RECIST V1.1 standard (unless the investigator evaluates that the subject continues to have clinical benefit from continuing treatment, the subject may be allowed to continue treatment), and begins to receive new anti-tumor treatment, unacceptable toxicity, withdrawal of informed consent, or other conditions that meet the criteria for terminating trial treatment / withdrawal from the trial. The research phase of this study is divided into pre-screening period (\~ D-28), screening period (D-28 \~ D-1), treatment period, treatment end visit (± 7 days after the last dose), safety follow-up ( Until 28 ± 7 days after the last dose) and survival follow-up.

Conditions

Esophageal Cancer

Keywords

ESCC;; EGFR overexpression;; Phase 3

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Defined as time from date of randomization to date of death due to any cause. OS was calculated using product-limit (Kaplan-Meier) method for censored data.

  up to approximately 22 months

Secondary Outcomes (7)

• Progression-free survival

  up to approximately 22 months

• Objective response rate

  up to approximately 22 months

• Duration of response

  up to approximately 22 months

• Changes in health-related quality of life with esophageal cancer symptom scale

  up to approximately 22 months

• Incidence of Treatment-Emergent Adverse Events

  up to approximately 22 months

Study Arms (2)

Lerotinib Arm

EXPERIMENTAL

350 mg,qd, orally about half an hour after a meal, continuous administration, every 21 days for a treatment cycle.

Drug: Lerotinib

Active Comparator Arm

ACTIVE COMPARATOR

Irinotecan: Intravenously administered at a dose of 180 mg/m2 every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Tegafur: 40-60mg po bid(d1-d14),every 21 days as a cycle, continuous drug administration from 1 to 14 days of each cycle, and then stopped 7 days.

Drug: Irinotecan/Tegafur

Interventions

Lerotinib DRUG

Specification: 50 mg/capsule and 150 mg/capsule

Also known as: Z650

Lerotinib Arm

Irinotecan/Tegafur DRUG

Irinotecan:Specification: 2mL: 40mg;5mL:0.1g Tegafur:20mg/capsule

Also known as: Irinotecan Hydrochloride Injection/Tegafur Gimeracil Oteracil Potassium Capsule

Active Comparator Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age:18-75 years, male or female.
• Histologically or cytologically confirmed squamous cell carcinoma of the esophagus or advanced/metastatic disease.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of greater than 3 months.
• Documented objective radiographic or clinical disease progression on two previous lines of standard therapy.
• Can provide archival tumor tissue sample for biomarker analysis (such as EGFR overexpression/expansion status), biopsies are required if tissue samples cannot be provided
• Confirmed by the central laboratory as EGFR high expression.
• Evaluable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
• Ability to swallow drugs.
• Adequate organ function.
• Voluntarily join the study and sign informed consent ad has good compliance.

You may not qualify if:

• Prior therapies with EGFR targeted drugs including EGFR antibodies.
• Previously treated with Irinotecan and Tegafur.
• Anthracycline, nitrosourea, and mitomycin within 6 weeks; traditional Chinese medicine for anti-tumor within 2 weeks;immune anti-tumor therapy. within 8 weeks;other anti-tumor therapies within 4 weeks before randomization.
• Not recovered from adverse events due to a previously administered agent.
• Have undergone major surgery within 4 weeks prior to randomization (not including diagnostic surgery) or expect major surgery during the study period.
• Previously or currently participating in other clinical trials within 4 weeks before randomization (subjects who have entered the follow-up period are calculated based on the last use of experimental drugs or devices).
• Received a live vaccine within 28 days before randomization or plan to receive live vaccine after enrollment.
• Received a strong inducer or inhibitor of CYP3A4 enzyme within 1 week or received Solivudine or its structurally similar drugs within 56 days prior to randomization.
• Simultaneously receiving any other anti-tumor treatment.
• Has a known additional malignancy previously within the last 5 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin or any other tumor that has been cured。
• Central nervous system metastasis or uncontrolled central nervous system metastasis currently in need of treatment; or confirmed central nervous system metastasis, but not stable for more than 4 weeks after anti-tumor therapy; spinal cord compression, cancerous meningitis, or meningitis.
• Clinically obvious gastrointestinal abnormalities, which may affect the intake, transport or absorption of drugs.
• Having active gastrointestinal ulcer, active gastrointestinal bleeding, and perforation;
• Risk of major bleeding or esophageal fistula;
• Previous or present with interstitial lung disease or immunotherapy-associated pneumonia; currently suffering from drug-induced pneumonia, radiation pneumonitis requiring steroid therapy, or clinically symptomatic active pneumonia, or other moderate to severe lungs that seriously affect lung function disease

Sponsors & Collaborators

• Sunshine Lake Pharma Co., Ltd.: lead

Study Sites (1)

Chinese PLA General Hospital

Beijing, Beijing Municipality, 100036, China

RECRUITING

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

Irinotecan; Tegafur

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• JianMing Xu, Doctor

  Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

JianMing Xu, Doctor

CONTACT

010-66939843; jmxu2003@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2020
• First Posted: June 4, 2020
• Study Start: January 21, 2021
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: May 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)