Immunotherapy in Combination With Chemoradiotherapy in Unresectable Locally Advanced Esophageal Cancer

NCT06173986 | Recruiting Phase 1

• 1 other identifier: SCR-ESCC-02
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Esophageal Squamous Cell Carcinoma; Unresectable Locally Advanced Esophageal Cancer

Keywords

Immunotherapy; Induction immunochemotherapy; Concurrent Immuno-Chemoradiotherapy; Unresectable locally advanced esophageal cancer; Esophageal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Progression-free survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first

  Assessed up to 60 months

• Treatment completion rate

  The Treatment Completion Rate is defined as the percentage of patients who successfully completed concurrent immuno-chemoradiotherapy.

  1 year

Secondary Outcomes (3)

• Objective response rate

  1 year

• Overall survival

  Assessed up to 60 months

• Incidence of Adverse events (AE) or severe adverse events (SAE)

  1 year

Study Arms (1)

IC+ICRT group

EXPERIMENTAL

2 cycles of PD-1 inhibitor + nab-paclitaxel + cisplatin followed by concurrent PD-1 inhibitor + radiotherapy (45-50Gy/25fx) + nab-paclitaxel + cisplatin

Drug: PD-1inhibitor; Drug: nab-paclitaxel + cisplatin; Radiation: Radiotherapy

Interventions

PD-1inhibitor DRUG

PD-1 inhibitor, Q3W, until disease progression or unacceptable toxicity or treatment reaches 1 year

Also known as: Immunotherapy

IC+ICRT group

nab-paclitaxel + cisplatin DRUG

Induction phase: nab-paclitaxel + cisplatin, Q3W × 2 cycles; Concurrent ICRT phase: nab-paclitaxel + cisplatin, QW × 5 cycles

Also known as: Chemotherapy

IC+ICRT group

Radiotherapy RADIATION

Primary tumor and metastatic lymph nodes, DT:45-50Gy/25fx, starting within 4 weeks following the completion of the last induction immunochemotherapy cycle

IC+ICRT group

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Chest Hospital: lead

Study Sites (1)

Shanghai Chest Hospital

Shanghai, China

RECRUITING

Related Publications (9)

• 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: 10.1200/JCO.20.03697. Epub 2021 Jun 8.

  PMID: 34101496 BACKGROUND

• 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 randomised, placebo-controlled, phase 3 study. Lancet. 2021 Aug 28;398(10302):759-771. doi: 10.1016/S0140-6736(21)01234-4.

  PMID: 34454674 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

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 Clin Oncol. 2022 Apr 20;40(12):1301-1311. doi: 10.1200/JCO.21.01308. Epub 2022 Feb 2.

  PMID: 35108059 BACKGROUND

• Kelly RJ, Ajani JA, Kuzdzal J, Zander T, Van Cutsem E, Piessen G, Mendez G, Feliciano J, Motoyama S, Lievre A, Uronis H, Elimova E, Grootscholten C, Geboes K, Zafar S, Snow S, Ko AH, Feeney K, Schenker M, Kocon P, Zhang J, Zhu L, Lei M, Singh P, Kondo K, Cleary JM, Moehler M; CheckMate 577 Investigators. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med. 2021 Apr 1;384(13):1191-1203. doi: 10.1056/NEJMoa2032125. Erratum In: N Engl J Med. 2023 Feb 16;388(7):672. doi: 10.1056/NEJMx220014.

  PMID: 33789008 BACKGROUND

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Immunotherapy; 130-nm albumin-bound paclitaxel; Cisplatin; Drug Therapy; Radiotherapy

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)

Immunomodulation; Biological Therapy; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Wen Yu, M.D

  Shanghai Chest Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wen Yu, M.D

CONTACT

021-22200000-3203; yuzhiwen0827@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Director of Radiation Oncology Department

Study Record Dates

• First Submitted: December 8, 2023
• First Posted: December 18, 2023
• Study Start: January 10, 2023
• Primary Completion: December 30, 2025
• Study Completion (Estimated): December 30, 2027
• Last Updated: December 18, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)