Immunotherapy in Combination With Chemoradiotherapy in Unresectable Locally Advanced Esophageal Cancer

Official title

A Phase I/II Multicenter Study Evaluating the Efficacy and Safety of Induction Immunochemotherapy Followed by Concurrent Immuno-Chemoradiotherapy in Unresectable Locally Advanced Esophageal Squamous Cell Cancer(SCR-ESCC-02)

Overview

SCR-ESCC-02 is a multicenter, phase I/II clinical study to investigate the safety and efficacy of induction immunochemotherapy followed by concurrent chemoradiotherapy with anti-PD-1 therapy in patients diagnosed with locally advanced, unresectable esophageal cancer.

Detailed description

Immunotherapy has shown promising results in advanced esophageal cancer, but its optimal integration into the management of unresectable locally advanced disease remains uncertain. The significant tumor regression and reduced tumor residual achieved through immunochemotherapy offer an opportunity to enhance the effectiveness of subsequent radiotherapy. This phase I/II clinical study aims to investigate the efficacy and safety of induction immunochemotherapy followed by concurrent chemoradiotherapy with anti-PD-1 for patients with unresectable locally advanced esophageal cancer. The study's co-primary endpoints are progression-free survival (PFS) and treatment completion rate.

Interventions

• Drug PD-1inhibitor
  PD-1 inhibitor, Q3W, until disease progression or unacceptable toxicity or treatment reaches 1 year
• Drug nab-paclitaxel + cisplatin
  Induction phase: nab-paclitaxel + cisplatin, Q3W × 2 cycles; Concurrent ICRT phase: nab-paclitaxel + cisplatin, QW × 5 cycles
• Radiation Radiotherapy
  Primary tumor and metastatic lymph nodes, DT:45-50Gy/25fx, starting within 4 weeks following the completion of the last induction immunochemotherapy cycle

Primary outcome measures

• Progression-free survival [Time frame: Assessed up to 60 months]
• Treatment completion rate [Time frame: 1 year]

Secondary outcome measures (3)

• Objective response rate [Time frame: 1 year]
• Overall survival [Time frame: Assessed up to 60 months]
• Incidence of Adverse events (AE) or severe adverse events (SAE) [Time frame: 1 year]

Eligibility criteria

Inclusion criteria

• Age between 18 and 75 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Clinical stage meeting the criteria of T1N+M0 or T2-4aN0-3M0 based on the 8th UICC-TNM classification.
• Ineligibility for surgical resections due to patients' unwillingness for surgery, technically unresectable disease, or being medically unfit for surgery.
• No prior anti-tumor treatment, including surgery, radiotherapy, chemotherapy, immunotherapy, or targeted therapy.
• Adequate hematological, pulmonary, cardiac, hepatic, renal, and thyroid function.
• Willingness to use contraception with an adequate method throughout the study.
• Documented informed consent.

Exclusion criteria

• History of malignant disease within the 5 years preceding enrollment or presence of other malignant tumors or non-squamous cell carcinoma components.
• High risk of gastrointestinal bleeding, esophageal fistula, or esophageal perforation as determined by the investigators.
• Weight loss exceeding 20% within the 90 days prior to the first day of drug administration.
• Presence of long-standing unhealed wounds or fractures or undergoing major surgical resections within 60 days preceding the first day of drug administration.
• Presence of any severe or uncontrolled coexisting diseases, including but not limited to:

• Uncontrolled hypertension
• History of interstitial lung disease or non-infectious pneumonia
• Active hepatitis B or C, syphilis, or other active and uncontrolled infections
• Cardiac insufficiency (NYHA≥2)
• Renal dysfunction requiring dialysis
• Active autoimmune disease
• History of acquired or congenital immunodeficiency diseases
• Occurrence of serious arterial/venous thrombotic events within 6 months prior to the first day of drug administration.
• History of psychotropic substance abuse or inability to quit, or patients with psychotic disorders.
• Allergy to study drugs.
• Patients deemed unsuitable for participation due to severe comorbidities or other reasons determined by the investigators.

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 Chest Hospital — Shanghai

Publications

• Hulshof MCCM, Geijsen ED, Rozema T, Oppedijk V, Buijsen J, Neelis KJ, Nuyttens JJME, van der Sangen MJC, Jeene PM, Reinders JG, van Berge Henegouwen MI, Thano A, van Hooft JE, van Laarhoven HWM, van der Gaast A. Randomized Study on Dose Escalation in Definitive Chemoradiation for Patients With Locally Advanced Esophageal Cancer (ARTDECO Study). J Clin Oncol. 2021 Sep 1;39(25):2816-2824. doi: 10.12 PMID 34101496
• Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, Metges JP, Li Z, Kim SB, Cho BC, Mansoor W, Li SH, Sunpaweravong P, Maqueda MA, Goekkurt E, Hara H, Antunes L, Fountzilas C, Tsuji A, Oliden VC, Liu Q, Shah S, Bhagia P, Kato K; KEYNOTE-590 Investigators. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a PMID 34454674
• 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
• Zhu Y, Wen J, Li Q, Chen B, Zhao L, Liu S, Yang Y, Wang S, Lv Y, Li J, Zhang L, Hu Y, Liu M, Xi M. Toripalimab combined with definitive chemoradiotherapy in locally advanced oesophageal squamous cell carcinoma (EC-CRT-001): a single-arm, phase 2 trial. Lancet Oncol. 2023 Apr;24(4):371-382. doi: 10.1016/S1470-2045(23)00060-8. PMID 36990609
• Shah MA, Bennouna J, Doi T, Shen L, Kato K, Adenis A, Mamon HJ, Moehler M, Fu X, Cho BC, Bordia S, Bhagia P, Shih CS, Desai A, Enzinger P. KEYNOTE-975 study design: a Phase III study of definitive chemoradiotherapy plus pembrolizumab in patients with esophageal carcinoma. Future Oncol. 2021 Apr;17(10):1143-1153. doi: 10.2217/fon-2020-0969. Epub 2021 Feb 3. PMID 33533655
• Yu R, Wang W, Li T, Li J, Zhao K, Wang W, Liang L, Wu H, Ai T, Huang W, Li L, Yu W, Wei C, Wang Y, Shen W, Xiao Z. RATIONALE 311: tislelizumab plus concurrent chemoradiotherapy for localized esophageal squamous cell carcinoma. Future Oncol. 2021 Nov;17(31):4081-4089. doi: 10.2217/fon-2021-0632. Epub 2021 Jul 16. PMID 34269067
• Wang Z, Shao C, Wang Y, Duan H, Pan M, Zhao J, Wang J, Ma Z, Li X, Yan X. Efficacy and safety of neoadjuvant immunotherapy in surgically resectable esophageal cancer: A systematic review and meta-analysis. Int J Surg. 2022 Aug;104:106767. doi: 10.1016/j.ijsu.2022.106767. Epub 2022 Jul 14. PMID 35840049
• Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, Vansteenkiste JF, Garassino MC, Hui R, Quantin X, Rimner A, Wu YL, Ozguroglu M, Lee KH, Kato T, de Wit M, Kurata T, Reck M, Cho BC, Senan S, Naidoo J, Mann H, Newton M, Thiyagarajah P, Antonia SJ. Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. J Cl PMID 35108059

Identifiers

NCT: NCT06173986 · SCR-ESCC-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗