Neoadjuvant Immunotherapy Combined With Chemotherapy Sequenced With Endoscopic Resection for Esophageal Cancer (Endosurgery-02)

Official title

Safety and Feasibility of Neoadjuvant Immunotherapy Combined With Chemotherapy Sequenced With Endoscopic Resection for Esophageal Cancer (Endosurgery-02)

Overview

This single-center, prospective, single-arm study will evaluate whether giving neoadjuvant chemoimmunotherapy can safely shrink esophageal cancer and allow organ-preserving endoscopic removal in selected patients. Adults with esophageal cancer will receive at least two 3-week cycles of a PD-1 inhibitor (tislelizumab 200 mg on Day 1) plus carboplatin (AUC 3-5, Day 1) and nab-paclitaxel (≤260 mg/m², Day 1). During treatment, routine safety tests are performed. About 3-4 weeks after completing at least two cycles, participants undergo clinical reassessment with examinations and imaging (such as endoscopy, endoscopic ultrasound, PET/CT or CT of the neck, chest, and upper abdomen) to evaluate tumor shrinkage and possible spread. Tumor response is assessed using RECIST 1.1. If a clinical complete response is achieved without obvious nodal disease, endoscopic resection may be performed to preserve the esophagus; otherwise, patients may proceed to surgery or concurrent chemoradiation per clinical judgment. The study focuses on feasibility and safety of this organ-preserving approach and describes tumor responses after therapy. Potential benefits include tumor shrinkage and avoiding major surgery in selected cases; risks include side effects of standard chemotherapy/immunotherapy and procedure-related discomforts from biopsies or endoscopic treatments.

Interventions

• Drug Tislelizumab
  Fixed-dose anti-PD-1 monoclonal antibody 200 mg IV on Day 1 of each 3-week cycle (Q3W) as neoadjuvant therapy, administered before any local resection. Given for ≥2 cycles unless contraindicated. Used in combination with carboplatin and nab-paclitaxel in a single-arm regimen; no placebo or comparator.
• Drug Carboplatin
  Intervention Description: AUC 3-5 IV on Day 1, Q3W, for ≥2 cycles in combination with tislelizumab and nab-paclitaxel as neoadjuvant therapy.
• Drug Nab-paclitaxel
  ≤260 mg/m² IV on Day 1, Q3W (\~30-min infusion) for ≥2 cycles, combined with tislelizumab and carboplatin in the neoadjuvant regimen.
• Procedure Endoscopic resection
  Endoscopic resection (e.g., ESD/EFTR) performed 3-6 weeks after completing ≥2 neoadjuvant cycles only if clinical complete response (cCR) is achieved without clear nodal metastasis, based on endoscopy/EUS and imaging. Technique follows institutional standards with curative intent and margin assessment.
• Procedure Esophagectomy
  Standard surgical esophagectomy (McKeown/Ivor-Lewis procedures) for participants not meeting cCR criteria or deemed unsuitable for endoscopic resection after reassessment. Conducted per institutional standard of care, with lymphadenectomy as appropriate.
• Radiation Concurrent chemoradiation
  Concurrent chemoradiation per institutional standard for participants not eligible for endoscopic resection and managed non-surgically after reassessment. External-beam radiation delivered with concurrent platinum-taxane chemotherapy as clinically indicated; specific dose/fractionation per treating radiation oncologist.

Primary outcome measures

• Organ preservation rate [Time frame: Up to 12 months after completion of neoadjuvant therapy]
• Overall safety: incidence of Grade ≥3 adverse events related to drug, endoscopic procedures, surgery, or radiation [Time frame: Adverse event was assessed peri-procedural of drug-using, endoscopic procedures, surgery, or radiation up to 30 days]
• Two-year overall survival rate [Time frame: From Day 1 of the first neoadjuvant dose to 24 months]
• Biomarkers [Time frame: Baseline and the day 1 of endoscopy or surgery]

Eligibility criteria

Cohort A - Potentially resectable ESCC:

Inclusion Criteria：

• Age range: 18-80 years old;
• Patients diagnosed with esophageal squamous cell carcinoma (ESCC) through histopathological examination of biopsy tissues from the primary tumor;
• Patients with potentially resectable esophageal cancer confirmed by imaging and endoscopic examinations (T1b-3, N0, M0, with a tumor size not exceeding 5 cm and occupying less than 2/3 of the luminal circumference); Patients who have not received any antitumor treatment, including but not limited to surgery, radiotherapy, chemotherapy, immunotherapy, and targeted therapy;
• Patients with a preoperative Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
• Patients with a preoperative American Society of Anesthesiologists (ASA) physical status classification of I-III;
• Female patients of reproductive age should have a negative pregnancy test and be willing to use effective contraceptive methods during the study period;
• Patients who have signed the informed consent form.

Exclusion criteria

• Patients with potential tracheoesophageal fistula or aortoesophageal fistula;
• Patients with severe malnutrition or requiring tube feeding;
• Patients with other malignancies that have not been cured within the past 2 years (except for cured basal cell carcinoma of the skin and cured carcinoma in situ of the cervix);
• Patients with active autoimmune diseases or a history of autoimmune diseases or symptoms that require systemic corticosteroid treatment or anti-autoimmune drug therapy;
• Immunocompromised patients, or patients who are still receiving systemic steroids (prednisone > 10 mg/day or equivalent) or other forms of immunosuppressive therapy within 7 days before the first dose of neoadjuvant therapy in this study;
• Patients with active infections requiring systemic treatment within 7 days before the first neoadjuvant therapy in this study;
• Patients with a history of allogeneic organ or stem cell transplantation;
• Patients with allergies to drugs or related components involved in this study;
• Patients who are currently participating in any other clinical study.

Cohort B - Surgery-contraindicated ESCC:

Inclusion criteria

• Individuals aged above 18 years;
• Patients diagnosed with esophageal squamous cell carcinoma through histopathological examination of biopsy tissues from the primary tumor;
• Patients with esophageal cancer deemed as surgically contraindicated (including those with cervical esophageal cancer, surgical contraindications, those who refuse surgery, or those considered high-risk for esophagectomy, defined as having at least one of the following characteristics: (1) age over 75 years, (2) Charlson comorbidity index >= 2, (3) presence of moderate lung dysfunction, (4) malnutrition (with a body mass index below 18 kg/m\^2)), with a clinical staging of cT1b-3N0M0, a tumor size not exceeding 5 cm, and occupying less than 2/3 of the luminal circumference;
• Patients who have not undergone any antitumor treatment, including but not limited to surgery, radiotherapy, chemotherapy, immunotherapy, and targeted therapy;
• Female patients of reproductive age should have a negative pregnancy test and be willing to adopt effective contraceptive measures during the study period;
• Patients who have signed the informed consent form.

Exclusion criteria

• Patients with allergies to the drugs or related components involved in this study;
• Patients who are currently participating in any other clinical study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai Zhongshan Hospital — Shanghai

Publications

• Wu H, Leng X, Liu Q, Mao T, Jiang T, Liu Y, Li F, Cao C, Fan J, Chen L, Chen Y, Yao Q, Lu S, Liang R, Hu L, Liu M, Wan Y, Li Z, Peng J, Luo Q, Zhou H, Yin J, Xu K, Lan M, Peng X, Lan H, Li G, Han Y, Zhang X, Xiao ZJ, Lang J, Wang G, Xu C. Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma. Cancer Res. 2023 Sep 15;83(18):3131-3144. doi: 1 PMID 37433041
• Ajani JA, D'Amico TA, Bentrem DJ, Chao J, Corvera C, Das P, Denlinger CS, Enzinger PC, Fanta P, Farjah F, Gerdes H, Gibson M, Glasgow RE, Hayman JA, Hochwald S, Hofstetter WL, Ilson DH, Jaroszewski D, Johung KL, Keswani RN, Kleinberg LR, Leong S, Ly QP, Matkowskyj KA, McNamara M, Mulcahy MF, Paluri RK, Park H, Perry KA, Pimiento J, Poultsides GA, Roses R, Strong VE, Wiesner G, Willett CG, Wright C PMID 31319389
• NCT02551458
• Noordman BJ, Wijnhoven BPL, Lagarde SM, Boonstra JJ, Coene PPLO, Dekker JWT, Doukas M, van der Gaast A, Heisterkamp J, Kouwenhoven EA, Nieuwenhuijzen GAP, Pierie JEN, Rosman C, van Sandick JW, van der Sangen MJC, Sosef MN, Spaander MCW, Valkema R, van der Zaag ES, Steyerberg EW, van Lanschot JJB; SANO-study group. Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophagea PMID 29409469
• Zhang X, Eyck BM, Yang Y, Liu J, Chao YK, Hou MM, Hung TM, Pang Q, Yu ZT, Jiang H, Law S, Wong I, Lam KO, van der Wilk BJ, van der Gaast A, Spaander MCW, Valkema R, Lagarde SM, Wijnhoven BPL, van Lanschot JJB, Li Z. Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): a prospective multicenter diagnostic cohort study. BM PMID 32143580
• Noordman BJ, Spaander MCW, Valkema R, Wijnhoven BPL, van Berge Henegouwen MI, Shapiro J, Biermann K, van der Gaast A, van Hillegersberg R, Hulshof MCCM, Krishnadath KK, Lagarde SM, Nieuwenhuijzen GAP, Oostenbrug LE, Siersema PD, Schoon EJ, Sosef MN, Steyerberg EW, van Lanschot JJB; SANO study group. Detection of residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer (preSANO): PMID 29861116
• Ge F, Huo Z, Cai X, Hu Q, Chen W, Lin G, Zhong R, You Z, Wang R, Lu Y, Wang R, Huang Q, Zhang H, Song A, Li C, Wen Y, Jiang Y, Liang H, He J, Liang W, Liu J. Evaluation of Clinical and Safety Outcomes of Neoadjuvant Immunotherapy Combined With Chemotherapy for Patients With Resectable Esophageal Cancer: A Systematic Review and Meta-analysis. JAMA Netw Open. 2022 Nov 1;5(11):e2239778. doi: 10.1001/ PMID 36322089
• Wang J, Zhang K, Liu T, Song Y, Hua P, Chen S, Li J, Liu Y, Zhao Y. Efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced esophageal cancer: A meta-analysis. Front Oncol. 2022 Sep 5;12:974684. doi: 10.3389/fonc.2022.974684. eCollection 2022. PMID 36158679

Identifiers

NCT: NCT07317609 · ShanghaiZhongshanEndosurgery02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗