Neoadjuvant Therapy for Stage II-IVA Resectable Esophageal Squamous Cell

NCT06006650 | Recruiting Phase 2

• 1 other identifier: K202208-28
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 3

Brief Summary

The aim of this study was to investigate the efficacy and safety of pembrolizumab combined with albumin paclitaxel and cisplatin versus albumin paclitaxel and cisplatin or 5-fluorouracil and cisplatin in neoadjuvant therapy for stage II-IVa resectable esophageal squamous cell carcinoma. The study plans to enroll 114 eligible patients who will be randomly assigned in a 1:1:1 ratio to receive 3 cycles of neoadjuvant immunochemotherapy (pembrolizumab plus albumin paclitaxel and cisplatin;Pembrolizumab plus 5-fluorouracil and cisplatin) or chemotherapy alone (5-fluorouracil and cisplatin), followed by surgery 3 weeks later, followed by 16 cycles of adjuvant immunotherapy (pembrolizumab).Patients were followed up for efficacy and safety during treatment.Tumor evaluation will be performed at screening, after neoadjuvant therapy, before surgery, and after adjuvant therapy until objective disease progression is confirmed.

Conditions

Neoadjuvent; PD-1 Inhibitor; Chemotherapy; Esophageal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response rate (pCR)

  Pathologic complete response rate (pCR)

  up to 4 months

Secondary Outcomes (3)

• Major pathological response(MPR)

  up to 4 months

• Event free survival(EFS)

  up to 10 years

• Overall survival(OS)

  up to 10 years

Study Arms (3)

Pembrolizumab Plus Albumin Paclitaxel and Cisplatin

EXPERIMENTAL

Preoperative neoadjuvant (pembrolizumab 200mg, d1 intravenously, q3w+ albumin paclitaxel 100mg/m2, d1/d8/d15 intravenously, q3w+ cisplatin 75mg/m2, d1 intravenously, q3w) 3 cycles + surgery + 16 cycles of postoperative pembrolizumab adjuvant therapy

Drug: Pembrolizumab, Albumin Paclitaxel, 5-fluorouracil, Cisplatin

Pembrolizumab Plus 5-fluorouracil and Cisplatin

ACTIVE COMPARATOR

Preoperative neoadjuvant (pembrolizumab 200mg, d1 intravenously, q3w+ 5-fluorouracil 800mg/m2, d1-5 intravenously, q3w+ cisplatin 75mg/m2, d1 intravenously, q3w) 3 cycles + surgery + 16 cycles of postoperative pembrolizumab adjuvant therapy

Drug: Pembrolizumab, Albumin Paclitaxel, 5-fluorouracil, Cisplatin

5-fluorouracil and Cisplatin

ACTIVE COMPARATOR

Preoperative neoadjuvant (5-fluorouracil 800mg/m2, d1-5 intravenously, q3w+ cisplatin 75mg/m2, d1 intravenously, q3w) 3 cycles + surgery + 16 cycles of postoperative pembrolizumab adjuvant therapy

Drug: Pembrolizumab, Albumin Paclitaxel, 5-fluorouracil, Cisplatin

Interventions

Pembrolizumab, Albumin Paclitaxel, 5-fluorouracil, Cisplatin DRUG

Pembrolizumab, Albumin Paclitaxel, 5-fluorouracil, Cisplatin

5-fluorouracil and Cisplatin; Pembrolizumab Plus 5-fluorouracil and Cisplatin; Pembrolizumab Plus Albumin Paclitaxel and Cisplatin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathological diagnosis: esophageal squamous cell carcinoma. 2.18-75 years old; 3.Clinical stage II-IVa; 4.no prior antitumor therapy, such as immunotherapy or chemoradiotherapy; 5.ECOG PS score 0-1. 6.Organs function well:Hemoglobin ≥100g/L, white blood cell count ≥4\*10\^9/L or neutrophil count ≥2.5\*10\^9/L, platelet count ≥100\*10\^9/L, serum total bilirubin level ≤1.5 times the upper limit of normal, aspartate aminotransferase (AST) ≤2.5 times the upper limit of normal,Alanine aminotransferase (ALT) ≤2.5 times the upper limit of normal, serum creatinine level below the upper limit of normal or creatinine clearance rate ≥60ml/min, urea nitrogen ≤200mg/L, urinary protein \<+, if urinary protein +, 24-hour total protein must be \<500mg, blood glucose:In patients with normal-range and/or diabetes under treatment but stable glycemic control, pulmonary function: baseline FEV1 of at least 2L;If the baseline FEV1 was \<2L, the predicted FEV1 after surgery was \>800ml, and the cardiac function was: no myocardial infarction within 1 year;Unstable angina pectoris;Asymptomatic severe arrhythmias;The centerless function is incomplete; 7.Non-surgically sterilized women, or women of reproductive age, need to use a medically approved contraceptive method (such as an intrauterine device, birth control pill, or condom) during and for 3 months after the end of the study treatment period.Women of childbearing age who were not surgically sterilized had to have a negative serum or urine HCG test within 72 hours before study enrollment.And must be non-lactation period;For male patients with partners of women of childbearing age, effective methods of contraception should be used during the trial period and within 3 months after the last dose of treatment; 8.Sign an informed consent form.

You may not qualify if:

• Pathological findings suggest compound squamous cell carcinoma, including squamous adenocarcinoma, squamous cell carcinoma, carcinosarcoma, sarcomatoid carcinoma, etc.
• History of subtotal gastrectomy;
• accompanied by a second primary cancer;
• Tumor metabolic imaging prior to treatment suggested distant metastasis.
• people who have previously received chemoradiotherapy;
• preesophageal perforation signs
• pregnant women of reproductive age;
• Any active autoimmune disease or a history of autoimmune disease (such as autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism, etc.);
• People with the following active infectious diseases, including active tuberculosis, hepatitis, and known human immunodeficiency virus (HIV) infection;
• Someone who has a known or concomitant hemorrhagic disease or other uncontrollable disease that cannot be treated surgically;
• Physical examination or clinical trial findings that researchers believe could interfere with the outcome or put the patient at increased risk of treatment complications;
• A previous history of interstitial lung disease, drug-induced interstitial disease, radiation pneumonitis requiring hormone therapy, or any clinically documented active interstitial lung disease, and the presence of idiopathic pulmonary fibrosis on CT scan at baseline;Uncontrolled massive pleural or pericardial effusion;
• unstable systemic diseases (active infection, moderately severe chronic obstructive pulmonary disease (copd), poorly controlled hypertension, unstable angina and congestive heart failure, 6 months occurrence of myocardial infarction, drug control severe mental disorders, liver, kidney or other metabolic disease, nerve mental disease such as Alzheimer 's disease);
• Gastrointestinal dysfunction, malabsorption syndrome, active gastrointestinal ulcers;
• Previously treated with anti-PD-1 or anti-PD-L1 antibodies;

Sponsors & Collaborators

• Tang-Du Hospital: lead

Study Sites (3)

Tangdu Hospital of the Fourth Millitary Medical University

Xi'an, Shaanxi, 710038, China

RECRUITING

Hongtao Duan

Xi’an, Shanxi, 710038, China

RECRUITING

Tangdu Hospital, the Air Force Military University

Xi'an, 710038, China

RECRUITING

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

pembrolizumab; Fluorouracil; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Xiaolong Yan, MD

  Tang-Du Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaolong Yan, MD

CONTACT

029-847171569; yanxiaolong@fmmu.edu.cn

HongTao Duan, MD

CONTACT

029-847171569

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Thoracic Surgery at Tangdu Hospital, Air Force Medical University

Study Record Dates

• First Submitted: August 17, 2023
• First Posted: August 23, 2023
• Study Start: August 1, 2022
• Primary Completion (Estimated): December 31, 2031
• Study Completion (Estimated): December 31, 2031
• Last Updated: August 23, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)