Neoadjuvant Immunochemotherapy for Adenocarcinoma of the Esophagogastric Junction

NCT06469060 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: SCE2403
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators will conduct a prospective phase 2 study to evaluate the efficacy and safety of a modified neoadjuvant immunotherapy plus chemotherapy (one cycle of Tislelizumab monotherapy followed by four cycles of Tislelizumab plus Docetaxel, Oxaliplatin and Capecitabine) in patients with locally advanced resectable adenocarcinoma of the esophagogastric junction (AEG).

Conditions

Esophageal Cancer

Keywords

Adenocarcinoma; Esophagogastric Junction; Immunochemotherapy

Outcome Measures

Primary Outcomes (1)

• pCR rate

  The primary endpoint is a pCR rate, which is defined as the absence of any remaining tumor cells in both the main tumor and the nearby lymph nodes (ypT0N0) as per the AJCC 8th Edition TRG scoring system

  Through the study completion, an average of 12 months

Secondary Outcomes (6)

• MPR rate

  Through the study completion, an average of 12 months

• Event-free survival (EFS)

  Through the study completion, an average of 36 months

• Overall survival (OS)

  Through the study completion, an average of 36 months

• Adverse events and treatment-related adverse events

  Through the study completion, an average of 12 months

• R0 resection rate

  Through the study completion, an average of 12 months

Study Arms (1)

neoadjuvant anti-PD-1 with DOC chemotherapy

EXPERIMENTAL

Drug: Immuno-chemotherapy. Patients will receive neoadjuvant therapy (one cycle of Tislelizumab monotherapy followed by four cycles of Tislelizumab plus Docetaxel, Oxaliplatin and Capecitabine) followed by the esophagectomy.

Drug: neoadjuvant anti-PD-1 with DOC chemotherapy

Interventions

neoadjuvant anti-PD-1 with DOC chemotherapy DRUG

Patients were treated with one cycle of Tislelizumab 200 mg monotherapy on day 1\. At 3 weeks and with intervals of 3 weeks between each cycle (weeks 3, 6, 9 and 12), patients received a total of four combination cycles consisting of Tislelizumab 200 mg, docetaxel 50 mg m-2 and oxaliplatin 100 mg m-2 intravenously at the beginning of each cycle, plus oral capecitabine 850 mg m-2 twice daily on days 1-14 of each cycle.

neoadjuvant anti-PD-1 with DOC chemotherapy

Eligibility Criteria

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

You may qualify if:

• Subjects signed the informed consent and volunteered to participate in the study.
• Primary resectable, histologically confirmed Adenocarcinoma of the Esophagogastric junction (clinical stage T1-T4aN1-3M0 or T3-T4aN0M0, AJCC 8th).
• Expect to have R0 resection
• Age 18 or older.
• ECOG PS: 0\~1.
• Have not received any anti-tumor treatment for esophageal cancer in the past, including radiotherapy, chemotherapy, surgery, etc.
• No contraindications to surgery.
• Has sufficient organ function.
• Women of childbearing age must undergo a serological pregnancy test within 7 days before first administration. Women of childbearing age, or male subjects with childbearing age female partners, must take contraceptive measures from the first dose to six months after last administration.
• Good compliance, willing to comply with follow-up schedules.

You may not qualify if:

• \. Subjects have received or are receiving any of:
• anti-tumor interventions such as radiotherapy, chemotherapy, immunotherapy or other medications.
• Received systemic corticosteroid therapy (prednisone equivalence\> 10mg/d) or other immunosuppressive agents within the first 2 weeks prior to the first administration.
• live vaccine within 4 weeks before the first administration.
• other cancers instead of AEG
• non-resectable or metastatic AEG
• Subjects with other malignant tumors within 5 years before the first administration, but subjects with cervical carcinoma in situ, skin basal cell carcinoma, skin squamous cell carcinoma, and localized prostate cancer received radical surgery in situ that have received radical treatment and do not need other treatment can be included.
• \. Other criteria: Subjects have uncontrolled cardiovascular diseases, such as 1) heart failure ≥ NYHA class 2, 2) unstable angina 3) myocardial infarction within 1 year; 4) supraventricular or ventricular arrythmia that needs treatment Subjects with any known active autoimmune disease Pregnant or breastfeeding female Presence of allergy or hypersensitivity to investigational medications HIV positive or active hepatitis B (HbsAg positive and HBV-DNA ≥2000 IU/ml or ≥ 104 copies/mL) or active hepatitis C (HCV antibody positive) or active tuberculosis Investigators assessed there might be other factors that cause subjects to withdrawal.

Sponsors & Collaborators

• Shanghai Chest Hospital: lead

Study Sites (1)

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 200030, China

Location

Related Publications (8)

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  PMID: 31433515 BACKGROUND

• van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074-84. doi: 10.1056/NEJMoa1112088.

  PMID: 22646630 BACKGROUND

• Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Lohr C, Bernhard H, Schuch G, Rethwisch V, von Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Weniger J, Belle S, Gaiser T, Oduncu FS, Guntner M, Hozaeel W, Reichart A, Jager E, Kraus T, Monig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019 May 11;393(10184):1948-1957. doi: 10.1016/S0140-6736(18)32557-1. Epub 2019 Apr 11.

  PMID: 30982686 BACKGROUND

• Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, Wyrwicz L, Yamaguchi K, Skoczylas T, Campos Bragagnoli A, Liu T, Schenker M, Yanez P, Tehfe M, Kowalyszyn R, Karamouzis MV, Bruges R, Zander T, Pazo-Cid R, Hitre E, Feeney K, Cleary JM, Poulart V, Cullen D, Lei M, Xiao H, Kondo K, Li M, Ajani JA. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021 Jul 3;398(10294):27-40. doi: 10.1016/S0140-6736(21)00797-2. Epub 2021 Jun 5.

  PMID: 34102137 BACKGROUND

• Qiu MZ, Oh DY, Kato K, Arkenau T, Tabernero J, Correa MC, Zimina AV, Bai Y, Shi J, Lee KW, Wang J, Poddubskaya E, Pan H, Rha SY, Zhang R, Hirano H, Spigel D, Yamaguchi K, Chao Y, Wyrwicz L, Disel U, Cid RP, Fornaro L, Evesque L, Wang H, Xu Y, Li J, Sheng T, Yang S, Li L, Moehler M, Xu RH; RATIONALE-305 Investigators. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial. BMJ. 2024 May 28;385:e078876. doi: 10.1136/bmj-2023-078876.

  PMID: 38806195 BACKGROUND

• Shitara K, Rha SY, Wyrwicz LS, Oshima T, Karaseva N, Osipov M, Yasui H, Yabusaki H, Afanasyev S, Park YK, Al-Batran SE, Yoshikawa T, Yanez P, Dib Bartolomeo M, Lonardi S, Tabernero J, Van Cutsem E, Janjigian YY, Oh DY, Xu J, Fang X, Shih CS, Bhagia P, Bang YJ; KEYNOTE-585 investigators. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): an interim analysis of the multicentre, double-blind, randomised phase 3 study. Lancet Oncol. 2024 Feb;25(2):212-224. doi: 10.1016/S1470-2045(23)00541-7. Epub 2023 Dec 19.

  PMID: 38134948 BACKGROUND

• Salas-Benito D, Perez-Gracia JL, Ponz-Sarvise M, Rodriguez-Ruiz ME, Martinez-Forero I, Castanon E, Lopez-Picazo JM, Sanmamed MF, Melero I. Paradigms on Immunotherapy Combinations with Chemotherapy. Cancer Discov. 2021 Jun;11(6):1353-1367. doi: 10.1158/2159-8290.CD-20-1312. Epub 2021 Mar 12.

  PMID: 33712487 BACKGROUND

• Verschoor YL, van de Haar J, van den Berg JG, van Sandick JW, Kodach LL, van Dieren JM, Balduzzi S, Grootscholten C, IJsselsteijn ME, Veenhof AAFA, Hartemink KJ, Vollebergh MA, Jurdi A, Sharma S, Spickard E, Owers EC, Bartels-Rutten A, den Hartog P, de Miranda NFCC, van Leerdam ME, Haanen JBAG, Schumacher TN, Voest EE, Chalabi M. Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial. Nat Med. 2024 Feb;30(2):519-530. doi: 10.1038/s41591-023-02758-x. Epub 2024 Jan 8.

  PMID: 38191613 BACKGROUND

MeSH Terms

Conditions

Esophageal Neoplasms; Adenocarcinoma

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Zhigang Li, MD, PhD

CONTACT

+86-18960619260; zhigang.li@shsmu.edu.cn

Zhichao Liu, MD, PhD

CONTACT

+86-15622175948; liuzc1995@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Department of Thoracic Surgery

Study Record Dates

• First Submitted: June 16, 2024
• First Posted: June 21, 2024
• Study Start: June 19, 2024
• Primary Completion: June 30, 2025
• Study Completion (Estimated): June 30, 2027
• Last Updated: July 1, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)