Circulating Tumor DNA MRD-Guided Adjuvant Therapy for Curatively Resected Locally Advanced Esophageal Squamous Cell Carcinoma

NCT06914011 | Not Yet Recruiting Phase 3

• 1 other identifier: 2025-0183
• Study Type: interventional
• Target: 172
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study was a multicenter, randomized, phase 3 trial to determine whether adjuvant chemotherapy including tisleliizumab improves recurrence-free survival compared to follow-up alone without chemotherapy in patients with curatively resected esophageal squamous cell carcinoma.

Conditions

Esophageal Cancer

Outcome Measures

Primary Outcomes (1)

• Recurrence-free survival as assessed by the investigator

  Every 12weeks during the first two years after randomization then every 24weeks

  For 5 years after randomization

Secondary Outcomes (10)

• Overall survival

  For 5 years after randomization

• Distant metastasis-free survival

  For 5 years after randomization

• Locoregional Recurrence-free survival

  For 5 years after randomization

• Pattern of first recurrence

  For 5 years after randomization

• The incidence and severity of adverse events according to NCI-CTCAE v5.0

  From the time of the first administration up to 30 days after the last administration (up to 50 days if the last administration was at a 6-week interval)

Other Outcomes (5)

• • Lead time between ctDNA re-emergence and radiologic recurrence

  For 5 years after randomization

• • Association between ctDNA dynamics and patterns of recurrence (locoregional vs. distant)

  For 5 years after randomization

• • PD-L1 expression by IHC as a predictive biomarker for treatment efficacy

  For 5 years after randomization

Study Arms (2)

Adjuvant therapy arm

EXPERIMENTAL

For participants assigned the adjuvant therapy arm, those who underwent neoadjuvant chemoradiotherapy followed by surgery will receive adjuvant chemoimmunotherapy. For patients who underwent neoadjuvant chemotherapy followed by surgery, or upfront surgery without prior neoadjuvant therapy, the choice between Option 1 (adjuvant chemoradioimmunotherapy) and Option 2 (adjuvant chemoimmunotherapy) will be made at the investigator's discretion. Adjuvant chemoradioimmunotherapy.

Drug: Tislelizumab

Surveillance arm

NO INTERVENTION

Surveillance arm will be followed up without any adjuvant therapy, undergoing CT scans every 12 weeks during the first 2 years after randomization, and thereafter every 24 weeks until 5 years after randomization

Interventions

Tislelizumab DRUG

1. Option 1: adjuvant chemoradioimmunotherapy in the following sequence: * Cycle 1: Tislelizumab 200 mg iv D1, Paclitaxel 175 mg/m2 iv D1, and Carboplatin AUC 5 mg/mL/min iv D1, in a 3-week cycle for one cycle * Cycle 2: Concurrent radiotherapy (25 fractions of 1.8 Gy each, with 5 fractions per week) with Tislelizumab 200 mg iv D1, D22, Paclitaxel 50 mg/m2 iv D1, 8, 15, 22, 29, and Carboplatin AUC 2 mg/mL/min D1, 8, 15, 22, 29 * Cycle 3: Tislelizumab 200 mg iv D1, Paclitaxel 175 mg/m2 iv D1, and Carboplatin AUC 5 mg/mL/min iv D1, in a 3-week cycle for 1 cycle * Cycles 4-9: Tislelizumab 400 mg iv D1, in a 6-week cycle for six cycles 2. Option 2: adjuvant chemoimmunotherapy in the following sequence: * Cycles 1-4: Tislelizumab 200 mg iv D1, Paclitaxel 175 mg/m2 iv D1, and Carboplatin AUC 5 mg/mL/min iv D1, in a 3-week cycle for four cycles * Cycles 5-10: Tislelizumab 400 mg iv D1, in a 6-week cycle for six cycles

Also known as: Paclitaxel, Carboplatin

Adjuvant therapy arm

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Be willing and able to provide written informed consent. 2. Be ≥19 years of age on the day of signing the informed consent form. 3. Have ECOG performance status of 0 or 1 (Appendix 1). 4. Have a histologically confirmed diagnosis of squamous cell carcinoma of the esophagus
• Patients with tumors of mixed histology (i.e., squamous and non-squamous) are eligible if the predominant histological component is squamous, except when small cell or neuroendocrine elements are present.
• \. Must have completed surgical resection for localized disease, either with prior neoadjuvant therapy (chemotherapy or chemoradiotherapy) or without prior neoadjuvant therapy (i.e., upfront surgery), in accordance with the 8th edition of the AJCC staging system (Appendix 2). Exceptionally, cases with supraclavicular lymph node metastasis as the only M1 lesion are also eligible if the lymph node has been surgically removed.
• \. Must have undergone curative surgery (R0 resection) with negative margins on the resected specimen.
• \. Complete resection must have been performed between 4-16 weeks before randomization.
• \. Must have a documented disease-free status based on a complete physical examination and imaging studies within 4 weeks before randomization. Imaging studies must include CT scans (or MRI) of the chest, abdomen, and pelvis.
• \. Must provide tumor tissue from pre-treatment biopsy (i.e., a biopsy obtained prior to neoadjuvant therapy in cases where neoadjuvant therapy is followed by surgery) or from surgical specimens and baseline blood samples for post-surgery ctDNA-MRD measurement and biomarker analyses.
• For patients who underwent upfront surgery, surgical tissue is preferred.
• For those who received neoadjuvant therapy followed by surgery, pre-treatment biopsy tissue is required. If pre-treatment biopsy tissue is unavailable or inadequate, submission of surgical specimens may be permitted following approval by the Study Sponsor.
• A FFPE tumor specimen in a paraffin block or 20 (at least 10, with a thickness of 10 µm) freshly cut unstained FFPE slides, along with one H\&E-stained slide, must be submitted with the associated pathology report. If an insufficient number of slides is available, the decision on patient enrollment can be made in consultation with the Study Sponsor.
• Peripheral blood of approximately 4 mL must be collected for germline DNA analysis.
• Peripheral blood of approximately 20 mL must be collected between 3 to 12 weeks after curative surgery for ctDNA testing.
• \. Must be confirmed to have MRD-positive status via postoperative baseline ctDNA testing.
• \. Must have adequate major organ functions as demonstrated by the following laboratory results obtained within 14 days before randomization (these criteria must also be met within 7 days before initiating study treatment in the adjuvant therapy arm):
• Adequate bone marrow function defined by:

You may not qualify if:

• \. Documented recurrence of esophageal cancer before randomization following curative resection.
• \. Receipt of any treatment aimed at the resected esophageal cancer after curative surgery, including chemotherapy, targeted therapy, immunotherapy, radiotherapy, biologic therapy, investigational agent, or local therapies, except for procedures intended for palliative care (e.g., stent insertion, balloon dilatation, or feeding enterostomy).
• \. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) inhibitor, or any other drug targeting T-cell co-stimulation or checkpoint pathways.
• \. Active autoimmune disease requiring systemic treatment within the 2 years prior to study entry (i.e., using disease-modifying agents, corticosteroids, or immunosuppressive drugs).
• Replacement therapy (e.g., thyroxine for autoimmune-related hypothyroidism, insulin for type 1 diabetes mellitus, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• \. Condition requiring systemic treatment with corticosteroids (\>10 mg daily prednisone or equivalent) or any other form of immunosuppressive therapy within 14 days prior to study entry.
• Use of topical, ocular, intra-articular, intranasal, and inhaled corticosteroids is permitted if there is no active autoimmune disease.
• A short course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergens) is permitted.
• \. Receipt of a live vaccine within 28 days prior to study entry.
• COVID-19 vaccines are allowed except for any live vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• \. Active infection requiring systemic therapy within 14 days prior to study entry.
• \. History of severe hypersensitivity to paclitaxel, carboplatin, or any antibody products.
• \. Known history of, or any evidence of, interstitial lung disease, non-infectious pneumonitis, or pulmonary fibrosis diagnosed based on imaging or clinical findings.
• Subjects with radiation pneumonitis may be enrolled if radiation pneumonitis is stable (beyond the acute phase) and unlikely to recur.
• \. History of allogeneic stem cell or solid organ transplantation. 11. Malignancies other than esophageal cancer within the 3 years prior to study entry, except for malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \>90%), such as adequately treated non-melanoma skin cancer, superficial bladder cancer, or carcinoma in situ (e.g., cervix, breast, or prostate).

Sponsors & Collaborators

• Asan Medical Center: lead

Related Publications (4)

• Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Chen Z, Yang H, Wang J, Pang Q, Zheng X, Yang H, Li T, Lordick F, D'Journo XB, Cerfolio RJ, Korst RJ, Novoa NM, Swanson SJ, Brunelli A, Ismail M, Fernando HC, Zhang X, Li Q, Wang G, Chen B, Mao T, Kong M, Guo X, Lin T, Liu M, Fu J; AME Thoracic Surgery Collaborative Group. Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial. J Clin Oncol. 2018 Sep 20;36(27):2796-2803. doi: 10.1200/JCO.2018.79.1483. Epub 2018 Aug 8.

  PMID: 30089078 RESULT

• Shapiro J, van Lanschot JJB, Hulshof MCCM, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL, van Laarhoven HWM, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, Cuesta MA, Blaisse RJB, Busch ORC, Ten Kate FJW, Creemers GM, Punt CJA, Plukker JTM, Verheul HMW, Bilgen EJS, van Dekken H, van der Sangen MJC, Rozema T, Biermann K, Beukema JC, Piet AHM, van Rij CM, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A; CROSS study group. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1090-1098. doi: 10.1016/S1470-2045(15)00040-6. Epub 2015 Aug 5.

  PMID: 26254683 RESULT

• 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 RESULT

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 RESULT

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

tislelizumab; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Central Study Contacts

Sook Ryun Park, MD, Ph.D

CONTACT

82-2-3010-3206; srpark@amc.seoul.kr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 31, 2025
• First Posted: April 6, 2025
• Study Start: May 6, 2026
• Primary Completion (Estimated): June 28, 2031
• Study Completion (Estimated): May 30, 2034
• Last Updated: June 2, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share