Clinical trial NCT05978193: Radiotherapy Combined With Immunochemotherapy in Metastatic Esophageal Squamous Cell Carcinoma
Official title: First-line Anti-PD-1 Therapy Plus Chemotherapy With or Without Radiotherapy in Metastatic Esophageal Squamous Cell Carcinoma: A Phase II Multi-center, Randomized Trial (SCR-ESCC-01)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Esophageal Squamous Cell Carcinoma
Esophageal Cancer
Metastatic Esophageal Squamous Cell Carcinoma
Keywords: Immunotherapy
low-dose radiotherapy
Esophageal squamous cell carcinoma
Immunoradiotherapy
Lead sponsor: Shanghai Chest Hospital
Sponsor class: OTHER
First posted: 2023-08-07
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: In metastatic esophageal cancer, radiotherapy is often administered for palliative purposes to alleviate the symptom of dysphagia. Recent studies have shown that the combination of radiotherapy and immunotherapy may have a synergistic effect on treatment outcomes. The study aims to investigate the benefit of LDRT in combination with conventionally fractionated radiotherapy (CFRT) in improving the outcome of metastatic ESCC concurrently treated with first-line immunochemotherapy. The recruited patients will be randomly (1:1) assigned to receive either PD-1 inhibitor plus chemotherapy (paclitaxel and platinum regimen) (arm B) or in combination with LDRT and CFRT (arm A). The primary endpoint is median progression-free survival (PFS).

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. Non-squamous cell esophageal carcinoma or ESCC mixed with other pathological types of esophageal cancer;
2. Patients who are potentially curable with surgery as assessed by investigators;
3. Pleural metastasis or malignant pleural effusion, pericardial effusion;
4. Any prior anti-tumor therapy for esophageal cancer, i.e., surgery, radiotherapy, chemotherapy, or immunotherapy;
5. High risk of gastrointestinal bleeding, esophageal fistula, or perforation;
6. Patients with Patient-Generated Subjective Globe Assessment (PG-SGA) score≥9;
7. Unstable cardiac diseases or symptoms;
8. History of interstitial pulmonary disease, non-infectious pneumonitis; pulmonary fibrosis, or other uncontrolled acute pulmonary disease;
9. Active autoimmune disease or history of autoimmune disease;
10. Conditions of immunodeficiency or active infection requiring systemic therapy;
11. Pregnant or breastfeeding;
12. 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).

Primary outcomes:
measure: PFS
timeFrame: 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
Secondary outcomes:
measure: OS
timeFrame: From date of randomization until the date of death from any cause, assessed up to 36 months
measure: Incidence of Grade III and higher treatment-related adverse events
timeFrame: 1 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Ruijin Hospital
city: Shanghai
country: China
facility: Shanghai Chest Hospital
Study officials:
affiliation: Shanghai Chest Hospital
name: Wen Yu, M.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.