Neoadjuvant Immunotherapy Plus CRT Versus Neoadjuvant CRT for Locally Advanced Resectable ESCC

NCT04973306 | Recruiting Phase 2

• 1 other identifier: B2021-369R
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study was to evaluate the safety, feasibility and outcome of anti-PD-1 antibody (Tislelizumab, BeiGene) combined with neoadjuvant chemoradiotherapy versus neoadjuvant chemoradiotherapy followed by minimally invasive esophagectomy for locally advanced resectable esophageal squamous cell carcinoma (cII-III Stage) patient.

Conditions

Esophageal Squamous Cell Carcinoma Stage II; Esophageal Squamous Cell Carcinoma Stage III

Keywords

Esophageal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Pathological response rate(pCR)

  The resected specimen following neo-adjuvant treatment are assessed by using standardized work up of the resection specimen in the pathology department and standardized histological criteria for tumor regression grading. The degree of histomorphologic regression is clarified into four categories as follows: grade 1, no evidence of vital residual tumor cells (pathological complete response); grade 2, less than 10% vital residual tumor cells; grade 3, 10 to 50%; and grade 4, more than 50%.

  Up to the date of pathological reports obtained since the date of randomization, up to 12 months

• Overall survival(OS)

  Up to the date of death of any causes since the date of randomization, up to 36 months

Secondary Outcomes (8)

• Treatment related complications

  Up to 1 month after surgery since the data of randomization, up to 13 months

• Progression-free survival(PFS)

  Up to the date of disease recurrence since the date of randomization, up to 36 months

• R0 resection rate

  Up to the date of pathological reports obtained since the date of randomization, up to 12 months

• Number and Location of positive lymph nodes

  Up to the date of pathological reports obtained since the date of randomization, up to 12 months

• Overall Quality of life

  Up to the end of follow-up since the data of surgery, up to 36 months

Study Arms (2)

Neoadjuvant chemoradiotherapy combined with anti-PD-1 antibody

EXPERIMENTAL

Neoadjuvant chemoradiotherapy (NCRT) combined with tislelizumab is performed followed by Ivor-Lewis or Mckeown esophagectomy in enrolled patients.

Procedure: Neoadjuvant Chemoradiotherapy; Drug: Tislelizumab; Procedure: Ivor-Lewis or Mckeown Esophagectomy(Mckeown Esophagectomy recommended)

Neoadjuvant chemoradiotherapy

ACTIVE COMPARATOR

Neoadjuvant chemoradiotherapy (NCRT) is performed followed by Ivor-Lewis or Mckeown esophagectomy in enrolled patients.

Procedure: Neoadjuvant Chemoradiotherapy; Procedure: Ivor-Lewis or Mckeown Esophagectomy(Mckeown Esophagectomy recommended)

Interventions

Neoadjuvant Chemoradiotherapy PROCEDURE

Chemotherapy: carboplatin (AUC 2 mg/mL per min) and paclitaxel (50 mg/m2 of body-surface area) were administered intravenously for five cycles, starting on days 1, 8, 15, 22, and 29. For each cycle, Carboplatin and paclitaxel were administered 30 minutes apart. Radiotherapy: A total radiation dose of 41.4 Gy was given in 23 fractions of 1.8 Gy, 5 days per week (Radiotherapy was performed on the 2nd, 3rd, 4th, 5th, and 6th day in each cycle, and only 3 times in the 5th cycle)

Neoadjuvant chemoradiotherapy; Neoadjuvant chemoradiotherapy combined with anti-PD-1 antibody

Tislelizumab DRUG

Tislelizumab (200mg/time) was administered intravenously on the 1st and 22nd day. The intravenous injection lasts about 30 minutes (micropump is recommended, intravenous bolus is prohibited, duration should be not less than 20 minutes and not more than 60 minutes);

Also known as: anti-PD-1 antibody

Neoadjuvant chemoradiotherapy combined with anti-PD-1 antibody

Ivor-Lewis or Mckeown Esophagectomy(Mckeown Esophagectomy recommended) PROCEDURE

After neoadjuvant therapy, patients in groups receive Ivor-Lewis or Mckeown Esophagectomy (Mckeown Esophagectomy recommended)

Neoadjuvant chemoradiotherapy; Neoadjuvant chemoradiotherapy combined with anti-PD-1 antibody

Eligibility Criteria

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

You may qualify if:

• Histologically-confirmed esophageal squamous cell carcinoma and whose tissue samples were taken before treatment;
• Tumors of the esophagus are located in the thoracic cavity;
• Pre-treatment stage as clinical II-III (AJCC/UICC 8th Edition)
• Age is between 18 years and 75 years;
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and expected survival time ≥12 months;
• Adequate cardiac function. All patients should perform ECG, and those with a cardiac history or ECG abnormality should perform echocardiography with the left ventricular ejection fraction \> 50 %;
• Adequate respiratory function with FEV1≥1.2L, FEV1%≥50% and DLCO≥50% shown in pulmonary function tests ;
• Adequate bone marrow function (White Blood Cells \>4x10\^9 /L; Neutrophil \>2.0×10\^9 /L; Hemoglobin \> 90 g/L; platelets\>100x10\^9 /L);
• Adequate liver function (Total bilirubin \<1.5x Upper Level of Normal (ULN); Aspartate transaminase(AST) and Alanine transaminase (ALT) \<1.5x ULN);
• Adequate renal function (Glomerular filtration rate (CCr) \>60 ml/min; serum creatinine (SCr) ≤120 µmol/L);
• The patient has provided written informed consent and is able to understand and comply with the study;

You may not qualify if:

• Patients with histological non-squamous cell carcinoma;
• Patients with advanced non-operable or metastatic esophageal cancer;
• Pre-treatment stage as cM+, cN3 or cT4b(non-curatively-resectable verified by the local surgical investigator, AJCC/UICC 8th Edition) or cTis-1a, cT1bN0;
• Patients with another previous or current malignant disease which is likely to interfere with treatment or the assessment of response in the judgement of the local surgical investigator;
• Patients who have received or are receiving other chemotherapy, radiotherapy or targeted therapy;
• Patients with autoimmune diseases history;
• Recently or currently taking Glucocorticoids or Immunosuppressants;
• Patients who underwent immunotherapy in the past;
• Allergy to any antibody drugs or allergy to Paclitaxel and Carboplatin.
• Past or currently suffering from chronic or recurrent autoimmune diseases;
• Patients with active infection of immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); HIV seropositivity; HBV DNA or HCV RNA positive;
• Patients with organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation);
• Patients with severe systematic intercurrent disease, such as active infection or poorly controlled diabetes; coagulation disorders; hemorrhagic tendency or under treatment of thrombolysis or anticoagulant therapy;
• Any patient with a significant medical condition which is thought unlikely to tolerate the therapies. Such as cardiac disease (e.g. symptomatic coronary artery disease or myocardial infarction within last 12 months), clinically-significant lung disease, clinically-significant bone marrow, liver, renal function disorder;
• Pregnant or lactating women and fertile women who will not be using contraception during the trial;

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead
• Peking University Cancer Hospital & Institute: collaborator
• Shanghai Chest Hospital: collaborator
• First Affiliated Hospital of Wenzhou Medical University: collaborator
• Tianjin Medical University Cancer Institute and Hospital: collaborator
• Ningbo Medical Center Lihuili Hospital: collaborator
• The First People's Hospital of Changzhou: collaborator
• Zhongshan Hospital (Xiamen), Fudan University: collaborator
• Xuhui Central Hospital, Shanghai: collaborator
• Shanghai Minhang Central Hospital: collaborator
• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: collaborator
• Zhejiang Cancer Hospital: collaborator
• Sichuan Cancer Hospital and Research Institute: collaborator
• Tongji Hospital: collaborator
• Sun Yat-sen University: collaborator
• Shanghai Fifth People's Hospital: collaborator

Study Sites (1)

Shanghai Zhongshan Hospital

Shanghai, 200032, China

RECRUITING

Related Publications (9)

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• Liu S, Wen J, Yang H, Li Q, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Zhao L, Liu H, Hu Y, Liu M, Fu J, Xi M. Recurrence patterns after neoadjuvant chemoradiotherapy compared with surgery alone in oesophageal squamous cell carcinoma: results from the multicenter phase III trial NEOCRTEC5010. Eur J Cancer. 2020 Oct;138:113-121. doi: 10.1016/j.ejca.2020.08.002. Epub 2020 Aug 30.

  PMID: 32877795 BACKGROUND

• McDermott DF, Atkins MB. PD-1 as a potential target in cancer therapy. Cancer Med. 2013 Oct;2(5):662-73. doi: 10.1002/cam4.106. Epub 2013 Jul 21.

  PMID: 24403232 BACKGROUND

• Doi T, Piha-Paul SA, Jalal SI, Saraf S, Lunceford J, Koshiji M, Bennouna J. Safety and Antitumor Activity of the Anti-Programmed Death-1 Antibody Pembrolizumab in Patients With Advanced Esophageal Carcinoma. J Clin Oncol. 2018 Jan 1;36(1):61-67. doi: 10.1200/JCO.2017.74.9846. Epub 2017 Nov 8.

  PMID: 29116900 BACKGROUND

• Yamamoto S, Kato K. Immuno-oncology for esophageal cancer. Future Oncol. 2020 Nov;16(32):2673-2681. doi: 10.2217/fon-2020-0545. Epub 2020 Aug 11.

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• Huang J, Xu J, Chen Y, Zhuang W, Zhang Y, Chen Z, Chen J, Zhang H, Niu Z, Fan Q, Lin L, Gu K, Liu Y, Ba Y, Miao Z, Jiang X, Zeng M, Chen J, Fu Z, Gan L, Wang J, Zhan X, Liu T, Li Z, Shen L, Shu Y, Zhang T, Yang Q, Zou J; ESCORT Study Group. Camrelizumab versus investigator's choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2020 Jun;21(6):832-842. doi: 10.1016/S1470-2045(20)30110-8. Epub 2020 May 13.

  PMID: 32416073 BACKGROUND

• Liao XY, Liu CY, He JF, Wang LS, Zhang T. Combination of checkpoint inhibitors with radiotherapy in esophageal squamous cell carcinoma treatment: A novel strategy. Oncol Lett. 2019 Nov;18(5):5011-5021. doi: 10.3892/ol.2019.10893. Epub 2019 Sep 19.

  PMID: 31612012 BACKGROUND

• Li C, Zhao S, Zheng Y, Han Y, Chen X, Cheng Z, Wu Y, Feng X, Qi W, Chen K, Xiang J, Li J, Lerut T, Li H. Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). Eur J Cancer. 2021 Feb;144:232-241. doi: 10.1016/j.ejca.2020.11.039. Epub 2020 Dec 26.

  PMID: 33373868 BACKGROUND

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Neoadjuvant Therapy; tislelizumab; spartalizumab

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)

Combined Modality Therapy; Therapeutics

Study Officials

• Lijie Tan, MD

  Shanghai Zhongshan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2021
• First Posted: July 22, 2021
• Study Start: March 2, 2022
• Primary Completion: July 1, 2024
• Study Completion (Estimated): July 1, 2027
• Last Updated: June 30, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)