Induction Immuno-chemotherapy and Concurrent Chemoradiotherapy With or Without Apatinib in Unresectable, Locally Advanced Esophageal Squamous Cell Carcinoma

Esophageal Squamous Cell Carcinoma Clinical Trial

Official title:

Induction Immuno-chemotherapy and Concurrent Chemoradiotherapy With or Without Apatinib in Unresectable, Locally Advanced Esophageal Squamous Cell Carcinoma: a Open-label, Randomized, Controlled Phase II Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06281886
• Other study ID #: GASTO-10107
• Status: Recruiting
• Phase: Phase 2
• Start date: December 1, 2023
• Est. completion date: December 1, 2026

Study information

• Verified date: February 2024
• Source: Sun Yat-sen University
• Contact: Bo Qiu, Professor
• Phone: +862087343031
• Email: qiubo[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, randomized, controlled phase II study evaluating induction immuno-chemotherapy and concurrent chemoradiotherapy with or without apatinib in unresectable, locally advanced esophageal squamous cell carcinoma

Description:

This is an open-label, randomized, controlled phase II study evaluating induction immuno-chemotherapy and concurrent chemoradiotherapy with or without apatinib in unresectable, locally advanced esophageal squamous cell carcinoma. In this study, patients are 1:1 randomized to either the study group or the control group. Patients in the study group will receive apatinib during induction immuno-chemotherapy and concurrent chemoradiotherapy. Patients in the control group will receive induction immuno-chemotherapy and concurrent chemoradiotherapy alone.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 170
• Est. completion date: December 1, 2026
• Est. primary completion date: December 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Diagnosed with esophageal squamous cell carcinoma through pathological examination or cytological examination;

• Evaluated as locally advanced esophageal cancer that is unresectable through endoscopic ultrasound, imaging studies including barium swallow, CT scans of the neck, chest, and upper abdomen, MR imaging of the neck and chest, whole-body bone scan, or PET/CT, with staging ranging from T2-4, N0-3, M0-1 (M1 only includes patients with supraclavicular lymph node metastasis);

• Male or female aged between 18 and 80 years old;

• No prior chemotherapy, radiotherapy, surgery, targeted therapy, or immunotherapy;

• Expected survival of =12 weeks;

• ECOG performance status score of 0 or 1;

• Organ and bone marrow function meeting the following criteria: forced expiratory volume in 1 second (FEV1) =800 ml; absolute neutrophil count =1.5×109/L; platelet count =100×109/L; hemoglobin =90 g/L; serum creatinine clearance calculated according to the Cockcroft-Gault formula =50 mL/min (Cockcroft and Gault 1976); serum bilirubin =1.5 times the upper limit of normal (ULN); aspartate aminotransferase and alanine aminotransferase =2.5 times ULN;

• Signed and dated informed consent form is required before any study procedures are performed.

Exclusion Criteria:

• Participating in another clinical study concurrently, unless it is an observational (non-interventional) clinical study;

• Prior use of any targeted therapy or immunotherapy;

• Underwent major surgery (excluding vascular access) within 4 weeks before entering the study;

• Uncontrolled complications, including but not limited to persistent or active infections, symptomatic congestive heart failure, poorly controlled hypertension, unstable angina, arrhythmias, active peptic ulcer disease or gastritis, intestinal perforation, intestinal obstruction, active bleeding disorders, or psychiatric illness/social situations that would limit compliance with study requirements or impair the ability to provide written informed consent;

• Performance status score of 2-4;

• Any of the following organ and bone marrow dysfunctions: forced expiratory volume in 1 second (FEV1) <1000ml; absolute neutrophil count <1.5×109/L; platelet count <100×109/L; hemoglobin <90 g/L; serum creatinine clearance calculated according to the Cockcroft-Gault formula <50 mL/min (Cockcroft and Gault 1976); serum bilirubin >1.5 times the upper limit of normal (ULN); aspartate aminotransferase and alanine aminotransferase >2.5 times ULN;

• Conditions that may interfere with the assessment of the efficacy or safety of apatinib;

• Use of immunosuppressive drugs within 28 days before the first infusion of trastuzumab, excluding physiologic doses of inhaled corticosteroids; or systemic corticosteroids =10 mg/d of prednisone or equivalent;

• History of autoimmune diseases within the past 2 years;

• History of active or inflammatory bowel disease (such as Crohn's disease, ulcerative colitis);

• History of organ transplantation requiring immunosuppressive therapy;

• Receipt of attenuated live vaccines within 30 days before the study initiation or within 30 days after receiving trastuzumab;

• History of another primary malignancy within 5 years before starting trastuzumab, except adequately treated basal or squamous cell skin cancer or in situ cervical cancer;

• Pregnant or lactating females; or sexually active males or females of reproductive potential not using effective contraception methods.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Efficacy
• Esophageal Squamous Cell Carcinoma
• Toxicity

Intervention

Drug:
• Induction Immunotherapy-Toripalimab
Toripalimab 240mg iv. drip, Q3W, 2 cycles
• Induction Chemotherapy-Albumin-paclitaxel combined with cisplatin
Albumin-paclitaxel 260 mg/m2, administered on day 1, combined with cisplatin 25 mg/m2, administered on day 1,2,3.

Radiation:
• Radiotherapy
Thoracic radiotherapy at a total dose of 50Gy was delivered using the intensity modulated radiation therapy technique.

Drug:
• Apatinib
Oral apatinib 250mg once daily during induction therapy and concurrent chemoradiotherapy.
• Capecitabine
Oral capecitabine 1000 mg/m2, twice daily, on days 1-14, every 3 weeks, concurrently with radiotherapy

Locations

Country	Name	City	State
China	Sun yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (15)

Chi D, Chen B, Guo S, Bai K, Ma H, Hu Y, Li Q, Zhu Y. Oral maintenance therapy using apatinib combined with S-1/capecitabine for esophageal squamous cell carcinoma with residual disease after definitive chemoradiotherapy. Aging (Albany NY). 2021 Mar 10;13(6):8408-8420. doi: 10.18632/aging.202652. Epub 2021 Mar 10. — View Citation

Chu L, Chen Y, Liu Q, Liang F, Wang S, Liu Q, Yu H, Wu X, Zhang J, Deng J, Ai D, Zhu Z, Nie Y, Zhao K. A Phase II Study of Apatinib in Patients with Chemotherapy-Refractory Esophageal Squamous Cell Carcinoma (ESO-Shanghai 11). Oncologist. 2021 Jun;26(6):e925-e935. doi: 10.1002/onco.13668. Epub 2021 Feb 1. — View Citation

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Cooper JS, Guo MD, Herskovic A, Macdonald JS, Martenson JA Jr, Al-Sarraf M, Byhardt R, Russell AH, Beitler JJ, Spencer S, Asbell SO, Graham MV, Leichman LL. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA. 1999 May 5;281(17):1623-7. doi: 10.1001/jama.281.17.1623. — View Citation

Hu L, Kong Z, Meng Q, Wang J, Zhou M, Yu J, Jiang X. The Safety and Efficacy of Apatinib Treatment in Addition to Concurrent Chemoradiotherapy in Patients with Nonoperative Locally Advanced Esophageal Squamous Cell Carcinoma. Med Sci Monit. 2020 Nov 27;26:e927221. doi: 10.12659/MSM.927221. — View Citation

Hu L, Sun F, Sun Z, Ni X, Wang J, Wang J, Zhou M, Feng Y, Kong Z, Hua Q, Yu J. Apatinib enhances the radiosensitivity of the esophageal cancer cell line KYSE-150 by inducing apoptosis and cell cycle redistribution. Oncol Lett. 2019 Feb;17(2):1609-1616. doi: 10.3892/ol.2018.9803. Epub 2018 Dec 6. — View Citation

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. — View Citation

Meng X, Wu T, Hong Y, Fan Q, Ren Z, Guo Y, Yang X, Shi P, Yang J, Yin X, Luo Z, Xia J, Zhou Y, Xu M, Liu E, Jiang G, Li S, Zhao F, Ma C, Ma C, Hou Z, Li J, Wang J, Wang F. Camrelizumab plus apatinib as second-line treatment for advanced oesophageal squamous cell carcinoma (CAP 02): a single-arm, open-label, phase 2 trial. Lancet Gastroenterol Hepatol. 2022 Mar;7(3):245-253. doi: 10.1016/S2468-1253(21)00378-2. Epub 2022 Jan 6. — View Citation

Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, Okawara G, Rosenthal SA, Kelsen DP. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol. 2002 Mar 1;20(5):1167-74. doi: 10.1200/JCO.2002.20.5.1167. — View Citation

Shinoda M, Ando N, Kato K, Ishikura S, Kato H, Tsubosa Y, Minashi K, Okabe H, Kimura Y, Kawano T, Kosugi S, Toh Y, Nakamura K, Fukuda H; Japan Clinical Oncology Group. Randomized study of low-dose versus standard-dose chemoradiotherapy for unresectable esophageal squamous cell carcinoma (JCOG0303). Cancer Sci. 2015 Apr;106(4):407-12. doi: 10.1111/cas.12622. Epub 2015 Mar 9. — View Citation

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. — View Citation

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Wang J, Yu JP, Wang JL, Ni XC, Sun ZQ, Sun W, Nie B, Jiang JT, Sun SP, Wu CP. [Pathologic response and changes of serum VEGF during chemoradiotherapy may predict prognosis in non-surgical patients with esophageal carcinoma]. Zhonghua Zhong Liu Za Zhi. 2016 Aug;38(8):589-95. doi: 10.3760/cma.j.issn.0253-3766.2016.08.005. Chinese. — View Citation

Xu Y, Dong B, Zhu W, Li J, Huang R, Sun Z, Yang X, Liu L, He H, Liao Z, Guan N, Kong Y, Wang W, Chen J, He H, Qiu G, Zeng M, Pu J, Hu W, Bao Y, Liu Z, Ma J, Jiang H, Du X, Hu J, Zhuang T, Cai J, Huang J, Tao H, Liu Y, Liang X, Zhou J, Tao G, Zheng X, Chen M. A Phase III Multicenter Randomized Clinical Trial of 60 Gy versus 50 Gy Radiation Dose in Concurrent Chemoradiotherapy for Inoperable Esophageal Squamous Cell Carcinoma. Clin Cancer Res. 2022 May 2;28(9):1792-1799. doi: 10.1158/1078-0432.CCR-21-3843. — View Citation

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* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival rate	From the first day of treatment to the day of progression or the day of death.	1 year
Secondary	Overall survival	It was calculated from the first day of treatment to the day of death.	1 year
Secondary	Objective response rate	The proportion of patients evaluated as CR or PR	1 year
Secondary	Local-regional progression-free survival	Local-regional progression-free survival refers to the period from the initiation of treatment until the occurrence of progression in the primary site or locoregional lymph node regions.	1 year
Secondary	Incidence of Treatment-related Adverse Events	Adverse effects are graded according to the CTCAE 5.0 version, including multiple organs and tissues, such as gastrointestinal disease and symptom, cardiovascular disease, respiratory diseases and so on.	1 year
Secondary	Score of Quality of Life Questionnare-Core 30 (The European Organization for Reasearch and Treatment of Cancer)	The evaluation of life quality	1 year
Secondary	Distant metastasis-free survival	Distant metastasis-free survival refers to the period from the initiation of treatment until the appearance of metastasis in distant organs or tissues.	1 year