Safety and Efficacy of Neoadjuvant Immunochemotherapy in Elderly Patients With Resectable Esophageal Cancer

Prospective, Single-arm, Phase II Study of Nab-paclitaxel Plus Carboplatin in Combination With Sintilimab for Neoadjuvant Therapy in Elderly, Locally Advanced, Resectable Esophageal Squamous Cell Carcinoma.

We intend to conduct a prospective single-arm clinical study to explore the efficacy and safety of immunochemotherapy in neoadjuvant therapy in elderly patients with advanced esophageal squamous cell carcinoma. Most previous randomized controlled studies (such as the 5010 study) have excluded older patients ≥70 years of age. However, in the real world, elderly patients with esophageal cancer account for a large number of patients, and elderly people have many complications and poor tolerance to treatment, which limits the application of synchronous chemoradiotherapy in this group. There is no standard treatment plan for patients over 70 years old, and the purpose of this study is to explore the effectiveness and safety of neoadjuvant immunochemotherapy in the treatment of this group of elderly people.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Cancer
• Intervention / Treatment: Drug: Carboplatin; Drug: Nab paclitaxel; Drug: Sintilimab

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Chengdu, China
    • Recruiting
    • West-China Hospital
    • Contact: zhenyu ding; Phone Number: +86 85421104; Email: dingzhenyu@scu.edu.cn
    • Contact: Zhen Lin; Phone Number: +86 85421104; Email: linzhenzlk@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age: ≥70 years (no age limit, with super-elderly patients, such as those ≥80 years, the investigator will assess whether to include them based on the actual situation; gender is not restricted).
2. ECOG PS: 0-1 points; and G8 score ≥14 points. (Patients with G8 scores <14 points will undergo Comprehensive Geriatric Assessment (CGA), and the investigator will decide on inclusion based on the assessment results).
3. Pathologically confirmed esophageal squamous cell carcinoma.
4. No history of prior anti-tumor treatment.
5. Clinical stage is T2-4aN0M0 or T1-4aN+M0, and MDT evaluation deems the patient operable (AJCC staging eighth edition).

6. Adequate organ function:

   • Hematological tests (within 7 days, without the use of hematopoietic growth factors and transfusion): Granulocyte count ≥1.5×10^9/L, platelet count ≥80×10^9/L, hemoglobin ≥80g/L.
   • Biochemical tests: Total bilirubin ≤1.5×ULN (upper limit of normal), blood alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.5×ULN; creatinine clearance rate ≥60 mL/min (Cockcroft-Gault formula).
   • Coagulation function: INR or PT ≤1.5×ULN (upper limit of normal). If the subject is receiving anticoagulant therapy, PT within the designated range of anticoagulant drugs is acceptable.
   • Cardiac function assessment: Normal electrocardiogram or an abnormal electrocardiogram (deemed clinically insignificant by the investigator); cardiac Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF) ≥50%.
7. Willing to voluntarily participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up.

Exclusion Criteria:

1. Concurrent presence of other malignant tumors.
2. Active autoimmune diseases or a history of autoimmune diseases, such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (eligible after normal hormone replacement therapy).
3. Uncontrollable severe systemic diseases (involving the central nervous system, cardiovascular system, hematological system, digestive system, endocrine system, respiratory system, urogenital system, immune system, etc.) and patients with mental illness.
4. Severe cardiovascular events: heart failure (NYHA III-IV), myocardial infarction, unstable angina, severe arrhythmia, stroke, or cerebral hemorrhage within the last 6 months.
5. Congenital or acquired immunodeficiency (such as HIV infection), active hepatitis B (HBV-DNA ≥ 10^4 copies/mL) or hepatitis C (positive HCV antibodies, and HCV-RNA higher than the detection limit of the analysis method).
6. Allergy or intolerance to the investigational drug.
7. Other conditions deemed unsuitable for inclusion in this study by the investigator.

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pathological complete response rate	Within two months after surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
one-year Disease-free-survival rate	Within one year after surgery
Surgical Completion Rate	Within two months after surgery
R0 resection rate	Within two months after surgery
Incidence of Adverse events to Neoadjuvant and Surgical Treatment	From the start of treatment to three months after surgery

Collaborators and Investigators

• Sponsor: Sichuan University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: May 3, 2024
• First Submitted That Met QC Criteria: May 3, 2024
• First Posted (Actual): May 8, 2024

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 3, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: SichuanU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data that support the findings of this study are available from the West China Hospital of Sichuan University but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with the permission of West China Hospital of Sichuan University. If anyone wants to request the date of the study, please contact the author, Zhen Lin. E-mail: linzhenzlk@163.com.

Drug and device information, study documents

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