Radiotherapy Combined With Immunochemotherapy in Metastatic Esophageal Squamous Cell Carcinoma

NCT05978193 | Recruiting Phase 2 DMC

• 1 other identifier: SCR-ESCC-01
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

SCR-ESCC-01 is a multicenter, randomized, phase II study aiming to investigate the benefit of early involvement of low-dose radiotherapy(LDRT) and conventionally fractionated radiotherapy(CFRT) in the first-line anti-PD-1 based treatment of metastatic ESCC. It begins with a safety run-in phase, followed by a randomized controlled comparison against standard immunochemotherapy.

Conditions

Metastatic Esophageal Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Esophageal Cancer

Keywords

Immunotherapy; low-dose radiotherapy; Esophageal squamous cell carcinoma; Immunoradiotherapy

Outcome Measures

Primary Outcomes (2)

• PFS

  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 36 months

• Safety and Feasibility of the Combined Regimen (Safety Run-in Phase)

  Incidence of Treatment-Related Adverse Events (TRAEs) in the initial cohort.

  From start of treatment up to 30 days after the last dose.

Secondary Outcomes (2)

• OS

  From date of randomization until the date of death from any cause, assessed up to 36 months

• Incidence of Grade III and higher treatment-related adverse events

  1 year

Study Arms (3)

Arm A

EXPERIMENTAL

PD-1 inhibitor + Paclitaxel + Cisplatin/Carboplatin+ Low-dose radiotherapy (LDRT) + Conventionally fractionated radiotherapy (CFRT)

Radiation: LDRT+CFRT; Drug: Immunotherapy; Drug: Chemotherapy

Arm B

ACTIVE COMPARATOR

PD-1 inhibitor + Paclitaxel + Cisplatin/Carboplatin

Drug: Immunotherapy; Drug: Chemotherapy

Safety Run-in Cohort

EXPERIMENTAL

Single Arm, LDRT + CFRT + Immunochemotherapy

Radiation: LDRT+CFRT; Drug: Immunotherapy; Drug: Chemotherapy

Interventions

Immunotherapy DRUG

PD-1 inhibitor 200mg, Q3W, until disease progression or unacceptable toxicity or treatment reaches 2 years

Arm A; Arm B; Safety Run-in Cohort

Chemotherapy DRUG

Paclitaxel+ Cisplatin, Q3W × 4cycles or Paclitaxel+ Carboplatin, Q3W × 4 cycles

Arm A; Arm B; Safety Run-in Cohort

LDRT+CFRT RADIATION

LDRT: Primary tumor and all visible metastatic lesions, DT: 2Gy/2fx, d1-2, Q3W × 4 cycles ; CFRT: Primary tumor, DT:40-50Gy/20-25fx, starting from the 5th immunotherapy cycle

Arm A; Safety Run-in Cohort

Eligibility Criteria

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

You may qualify if:

• Age ≥18;
• Metastatic esophageal squamous cell carcinoma (stage IVB, M1) confirmed by pathology;
• ECOG performance status: 0-1 point;
• No prior anti-tumor treatment;
• Adequate hematologic, renal, hepatic, and cardiac functions that meet the requirements for chemotherapy and immunotherapy assessed by investigators.

You may not qualify if:

• Non-squamous cell esophageal carcinoma or ESCC mixed with other pathological types of esophageal cancer;
• Patients who are potentially curable with surgery as assessed by investigators;
• Pleural metastasis or malignant pleural effusion, pericardial effusion;
• Any prior anti-tumor therapy for esophageal cancer, i.e., surgery, radiotherapy, chemotherapy, or immunotherapy;
• High risk of gastrointestinal bleeding, esophageal fistula, or perforation;
• Patients with Patient-Generated Subjective Globe Assessment (PG-SGA) score≥9;
• Unstable cardiac diseases or symptoms;
• History of interstitial pulmonary disease, non-infectious pneumonitis; pulmonary fibrosis, or other uncontrolled acute pulmonary disease;
• Active autoimmune disease or history of autoimmune disease;
• Conditions of immunodeficiency or active infection requiring systemic therapy;
• Pregnant or breastfeeding;
• Patients with synchronous second primary cancer and a history of malignancy within the past 5 years (excluding completely cured cervical carcinoma in situ or basal cell or squamous cell skin carcinoma).

Sponsors & Collaborators

• Shanghai Chest Hospital: lead

Study Sites (2)

Shanghai Ruijin Hospital

Shanghai, 200020, China

RECRUITING

Shanghai Chest Hospital

Shanghai, 200030, China

RECRUITING

Related Publications (10)

• 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

• Luo H, Lu J, Bai Y, Mao T, Wang J, Fan Q, Zhang Y, Zhao K, Chen Z, Gao S, Li J, Fu Z, Gu K, Liu Z, Wu L, Zhang X, Feng J, Niu Z, Ba Y, Zhang H, Liu Y, Zhang L, Min X, Huang J, Cheng Y, Wang D, Shen Y, Yang Q, Zou J, Xu RH; ESCORT-1st Investigators. Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial. JAMA. 2021 Sep 14;326(10):916-925. doi: 10.1001/jama.2021.12836.

  PMID: 34519801 BACKGROUND

• Lu Z, Wang J, Shu Y, Liu L, Kong L, Yang L, Wang B, Sun G, Ji Y, Cao G, Liu H, Cui T, Li N, Qiu W, Li G, Hou X, Luo H, Xue L, Zhang Y, Yue W, Liu Z, Wang X, Gao S, Pan Y, Galais MP, Zaanan A, Ma Z, Li H, Wang Y, Shen L; ORIENT-15 study group. Sintilimab versus placebo in combination with chemotherapy as first line treatment for locally advanced or metastatic oesophageal squamous cell carcinoma (ORIENT-15): multicentre, randomised, double blind, phase 3 trial. BMJ. 2022 Apr 19;377:e068714. doi: 10.1136/bmj-2021-068714.

  PMID: 35440464 BACKGROUND

• Wang ZX, Cui C, Yao J, Zhang Y, Li M, Feng J, Yang S, Fan Y, Shi J, Zhang X, Shen L, Shu Y, Wang C, Dai T, Mao T, Chen L, Guo Z, Liu B, Pan H, Cang S, Jiang Y, Wang J, Ye M, Chen Z, Jiang D, Lin Q, Ren W, Wang J, Wu L, Xu Y, Miao Z, Sun M, Xie C, Liu Y, Wang Q, Zhao L, Li Q, Huang C, Jiang K, Yang K, Li D, Liu Y, Zhu Z, Chen R, Jia L, Li W, Liao W, Liu HX, Ma D, Ma J, Qin Y, Shi Z, Wei Q, Xiao K, Zhang Y, Zhang Y, Chen X, Dai G, He J, Li J, Li G, Liu Y, Liu Z, Yuan X, Zhang J, Fu Z, He Y, Ju F, Liu Z, Tang P, Wang T, Wang W, Zhang J, Luo X, Tang X, May R, Feng H, Yao S, Keegan P, Xu RH, Wang F. Toripalimab plus chemotherapy in treatment-naive, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-center phase 3 trial. Cancer Cell. 2022 Mar 14;40(3):277-288.e3. doi: 10.1016/j.ccell.2022.02.007. Epub 2022 Mar 3.

  PMID: 35245446 BACKGROUND

• Herrera FG, Bourhis J, Coukos G. Radiotherapy combination opportunities leveraging immunity for the next oncology practice. CA Cancer J Clin. 2017 Jan;67(1):65-85. doi: 10.3322/caac.21358. Epub 2016 Aug 29.

  PMID: 27570942 BACKGROUND

• Shaverdian N, Lisberg AE, Bornazyan K, Veruttipong D, Goldman JW, Formenti SC, Garon EB, Lee P. Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. Lancet Oncol. 2017 Jul;18(7):895-903. doi: 10.1016/S1470-2045(17)30380-7. Epub 2017 May 24.

  PMID: 28551359 BACKGROUND

• Theelen WSME, Peulen HMU, Lalezari F, van der Noort V, de Vries JF, Aerts JGJV, Dumoulin DW, Bahce I, Niemeijer AN, de Langen AJ, Monkhorst K, Baas P. Effect of Pembrolizumab After Stereotactic Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients With Advanced Non-Small Cell Lung Cancer: Results of the PEMBRO-RT Phase 2 Randomized Clinical Trial. JAMA Oncol. 2019 Sep 1;5(9):1276-1282. doi: 10.1001/jamaoncol.2019.1478.

  PMID: 31294749 BACKGROUND

• Herrera FG, Ronet C, Ochoa de Olza M, Barras D, Crespo I, Andreatta M, Corria-Osorio J, Spill A, Benedetti F, Genolet R, Orcurto A, Imbimbo M, Ghisoni E, Navarro Rodrigo B, Berthold DR, Sarivalasis A, Zaman K, Duran R, Dromain C, Prior J, Schaefer N, Bourhis J, Dimopoulou G, Tsourti Z, Messemaker M, Smith T, Warren SE, Foukas P, Rusakiewicz S, Pittet MJ, Zimmermann S, Sempoux C, Dafni U, Harari A, Kandalaft LE, Carmona SJ, Dangaj Laniti D, Irving M, Coukos G. Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy. Cancer Discov. 2022 Jan;12(1):108-133. doi: 10.1158/2159-8290.CD-21-0003. Epub 2021 Sep 3.

  PMID: 34479871 BACKGROUND

• Yin L, Xue J, Li R, Zhou L, Deng L, Chen L, Zhang Y, Li Y, Zhang X, Xiu W, Tong R, Gong Y, Huang M, Xu Y, Zhu J, Yu M, Li M, Lan J, Wang J, Mo X, Wei Y, Niedermann G, Lu Y. Effect of Low-Dose Radiation Therapy on Abscopal Responses to Hypofractionated Radiation Therapy and Anti-PD1 in Mice and Patients With Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2020 Sep 1;108(1):212-224. doi: 10.1016/j.ijrobp.2020.05.002. Epub 2020 May 15.

  PMID: 32417411 BACKGROUND

• Li Y, Lin L, Liu J, Cai XW, Zhang Q, Song XY, Zhao SG, Ma XM, Fu XL, Yu W. Phase II multicenter trial: first-line immunochemotherapy with or without radiotherapy in metastatic esophageal squamous cell cancer (SCR-ESCC-01). Future Oncol. 2023 Nov;19(34):2291-2296. doi: 10.2217/fon-2023-0674. Epub 2023 Nov 8.

  PMID: 37937444 DERIVED

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma; Esophageal Neoplasms

Interventions

Immunotherapy; Drug Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; 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

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 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Director of Radiation Oncology Department

Model Details: Includes a single-arm safety run-in followed by randomization.

Study Record Dates

• First Submitted: July 28, 2023
• First Posted: August 7, 2023
• Study Start: January 1, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)