Tucidinostat Plus PD-1 Inhibitor and Bevacizumab for Advanced Esophagus Cancer, AEG, Gastric Cancer

Tucidinostat in Combination With PD-1 Inhibitor and Bevacizumab as Late-line Treatment in Patients With Advanced Esophageal Squamous Cell Cancer, Adenocarcinoma of Esophagogastric Junction and Gastric Adenocarcinoma

This Phase II study was designed to assess the efficacy and safety of the combination of PD-1 inhibitor, Tucidinostat (chidamide), a histone deacetylase inhibitor, and bevacizumab in advanced Esophageal squamous cell cancer, adenocarcinoma of esophagogastric junction, Gastric adenocarcinoma patients.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Squamous Cell Cancer, Adenocarcinoma of Esophagogastric Junction, Gastric Adenocarcinoma
• Intervention / Treatment: Drug: Tucidinostat (chidamide), PD-1 inhibitor (Toripalimab), Bevacizumab

• Study Type: Interventional
• Enrollment (Anticipated): 87
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Cancer center of Sun Yat-sen University
      • Sub-Investigator: Fenghua Wang, MD, PhD
      • Sub-Investigator: Miaozhen Qiu, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥18 years, ≤ 75 years
2. Histologically or cytologically confirmed Esophageal squamous cell cancer, adenocarcinoma of esophagogastric junction and Gastric adenocarcinoma, unresectable, recurrent or metastatic disease.
3. Can provide at least 5 pieces of pathological section or fresh tumor tissue
4. Eastern Collaborative Oncology Group (ECOG) ≤ 1.
5. ≤2 systemic chemotherapy for advanced disease (total number of treatment lines for advanced disease ≤4).
6. Patients who have previously used PD-1 antibodies, PD-L1 antibodies, PD-L2 antibodies, or CTLA-4 antibodies (or any other antibodies acting on T cell co-stimulation or checkpoint pathways) or require a duration of ≥16 weeks;
7. Adequate organ function.
8. Life expectancy is more than 3 months.
9. For females of child bearing potential, a negative urine or serum pregnancy test result within 3 days before study treatment.
10. Willing and able to provide written informed consent.

Exclusion Criteria:

1. Allergies to any monoclonal antibody or Tucidinostat preparation have been known, and hypersensitivity reactions of more than 3 levels have occurred
2. Previously received immunotherapy and had grade 3 or above immune-related adverse events.
3. Previously received histone deacetylase inhibitors,or toripalimab, or angiogenesis inhibitors.
4. Subjects with any active, known or suspected autoimmune disease or history of autoimmune disease.
5. Known active CNS metastases and/or carcinomatous meningitis.
6. Received a live vaccine within 4 weeks of the first dose of study medication.
7. Major surgery received or severe traumatic injury, fracture, or ulcer occurred within 4 weeks of the first dose of study medication.
8. Pregnant or lactating female.
9. Uncontrolled clinically significant systemic diseases, including active infection, unstable angina, angina occurred within 3 months,≥ NYHA II congestive heart failure, myocardial infarction occurred within 6 months, severe arrhythmia, liver, kidney, or metabolic disease.
10. Participate in other clinical trials currently or within 4 weeks prior to enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tucidinostat (chidamide), PD-1 inhibitor （Toripalimab), Bevacizumab; Tucidinostat (chidamide), 30mg, po., biw, q3w Toripalimab, 240mg, ivgtt., d1, q3w Bevacizumab, 7.5mg/kg, ivgtt., d1, q3w approximately 2 years	Drug: Tucidinostat (chidamide), PD-1 inhibitor (Toripalimab), Bevacizumab; Tucidinostat (chidamide), 30mg, po., biw, q3w Toripalimab, 240mg, ivgtt., d1, q3w Bevacizumab, 7.5mg/kg, ivgtt., d1, q3w approximately 2 years; Other Names: Tucidinostat (chidamide) JS001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate（ORR）	Objective Response Rate（ORR）by RECIST 1.1,the total proportion of patients with complete response（CR）, partial response（PR）	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival(PFS)	Time from treatment until disease progression or death	2 years
Overall survival(OS)	Time from treatment until death from any cause	3 years
Disease Control Rate （DCR）	the total proportion of patients with complete response（CR）, partial response（PR）and stable disease（SD）	2 years
Duration of Response（DoR）	Time from the achievement of a response to progression	2 years

Collaborators and Investigators

• Sponsor: Ruihua Xu

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: December 15, 2021
• First Submitted That Met QC Criteria: December 15, 2021
• First Posted (Actual): December 20, 2021

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: March 2, 2023
• Last Verified: July 1, 2022

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; Adenocarcinoma; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Neoplasms, Squamous Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; Immune Checkpoint Inhibitors
• Other Study ID Numbers: CSIIT-Q24

Drug and device information, study documents

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