Toripalimab Plus Neoadjuvant Chemotherapy Combined With Chemoradiotherapy for Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma

Esophageal Squamous Cell Carcinoma Clinical Trial

Official title:

A Prospective Single-arm Phase Ⅱ Study of Toripalimab Plus Neoadjuvant Chemotherapy Combined With Chemoradiotherapy for Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04844385
• Other study ID #: GASTO-1071
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 20, 2021
• Est. completion date: December 20, 2024

Study information

• Verified date: February 2024
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase II non-randomized study is to determine the efficacy and toxicity of neoadjuvant toripalimab plus chemotherapy followed by chemoradiotherapy for locally advanced unresectable esophageal squamous cell carcinoma.

Description:

This Phase II non-randomized study is to determine the efficacy and toxicity of neoadjuvant toripalimab plus chemotherapy followed by chemoradiotherapy for locally advanced unresectable esophageal squamous cell carcinoma.

All patients were planned to receive 2 cycle of toripalimab plus paclitaxel/nedaplatin as neoadjuvant therapy. Then they all receive radical dose of chest radiation and concurrent chemotherapy of capecitabine (PO 1000 mg/m2, bid, d1-d14, q3w).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 124
• Est. completion date: December 20, 2024
• Est. primary completion date: December 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• histologically confirmed esophageal squamous cell carcinoma

• patients have measurable or evaluable lesions based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria

• unresectable T1-4 N0-3 M0-1 confirmed by CT or MRI (M1 only includes patients with lymph node metastasis in the supraclavicular region)

• ECOG performance status 0-1

• no previous chest radiotherapy, immunotherapy or biotherapy.

• hemoglobin=10 mg/dL, platelet=100000/µL,absolute neutrophil count =1500/µL

• serum creatinine =1.25 times the upper normal limit(UNL), or creatinine clearance=60 ml/min

• bilirubin =1.5 times UNL, AST(SGOT)=2.5 times UNL ,ALT(SGPT)=2.5 times UNL,alkaline phosphatase =5 times UNL

• FEV1 >0.8 L

• CB6 within normal limits

• patients and their family signed the informed consents

Exclusion Criteria:

• previous or recent another malignancy, except for nonmelanoma skin cancer or cervical cancer in situ

• contraindication for chemotherapy

• women in pregnancy, lactation period, or no pregnancy test 14 days before the first dose

• women who has the probability of pregnancy without contraception

• tendency of hemorrhage

• in other clinical trials within 30 days

• addicted in drugs or alcohol, AIDS patients

• uncontrollable seizure or psychotic patients without self-control ability

• severe allergy or idiosyncrasy

• not suitable for this study judged by researchers

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma

Intervention

Drug:
• Toripalimab
Toripalimab 240 mg, d1, Q3w for two cycles
• Paclitaxel-albumin
Paclitaxel-albumin 260 mg/m2, d1, Q3w for two cycles
• Nedaplatin
Nedaplatin 75mg/m2, d1, Q3w for two cycles

Radiation:
• radiation therapy at a total dose 60 Gy
Radiation therapy at a total dose 60 Gy

Drug:
• Capecitabine
Capecitabine 1000 mg/m2, bid, d1-14, q3w during radiotherapy

Radiation:
• radiation therapy at a total dose 50 Gy
Radiation therapy at a total dose 50 Gy

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 (13)

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. Erratum In: CA Cancer J Clin. 2020 Jul;70(4):313. — View Citation

Butler EB, Teh BS, Grant WH 3rd, Uhl BM, Kuppersmith RB, Chiu JK, Donovan DT, Woo SY. Smart (simultaneous modulated accelerated radiation therapy) boost: a new accelerated fractionation schedule for the treatment of head and neck cancer with intensity modulated radiotherapy. Int J Radiat Oncol Biol Phys. 1999 Aug 1;45(1):21-32. doi: 10.1016/s0360-3016(99)00101-7. — View Citation

Chen Y, Ye J, Zhu Z, Zhao W, Zhou J, Wu C, Tang H, Fan M, Li L, Lin Q, Xia Y, Li Y, Li J, Jia H, Lu S, Zhang Z, Zhao K. Comparing Paclitaxel Plus Fluorouracil Versus Cisplatin Plus Fluorouracil in Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Cancer: A Randomized, Multicenter, Phase III Clinical Trial. J Clin Oncol. 2019 Jul 10;37(20):1695-1703. doi: 10.1200/JCO.18.02122. Epub 2019 Mar 28. — View Citation

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

Fan TY, Xing J, Lu J, Liu TH, Xu M, Zhang YJ, Shao Q, Li JB, Yu JM. Phase I/II study of induction chemotherapy plus concurrent chemotherapy and SMART-IMRT-based radiotherapy in locoregionally-advanced nasopharyngeal cancer. Oncol Lett. 2013 Mar;5(3):889-895. doi: 10.3892/ol.2013.1137. Epub 2013 Jan 15. — View Citation

Gaspar LE, Winter K, Kocha WI, Coia LR, Herskovic A, Graham M. A phase I/II study of external beam radiation, brachytherapy, and concurrent chemotherapy for patients with localized carcinoma of the esophagus (Radiation Therapy Oncology Group Study 9207): final report. Cancer. 2000 Mar 1;88(5):988-95. — View Citation

Kato K, Shah MA, Enzinger P, Bennouna J, Shen L, Adenis A, Sun JM, Cho BC, Ozguroglu M, Kojima T, Kostorov V, Hierro C, Zhu Y, McLean LA, Shah S, Doi T. KEYNOTE-590: Phase III study of first-line chemotherapy with or without pembrolizumab for advanced esophageal cancer. Future Oncol. 2019 Apr;15(10):1057-1066. doi: 10.2217/fon-2018-0609. Epub 2019 Feb 8. — View Citation

Kojima T, Shah MA, Muro K, Francois E, Adenis A, Hsu CH, Doi T, Moriwaki T, Kim SB, Lee SH, Bennouna J, Kato K, Shen L, Enzinger P, Qin SK, Ferreira P, Chen J, Girotto G, de la Fouchardiere C, Senellart H, Al-Rajabi R, Lordick F, Wang R, Suryawanshi S, Bhagia P, Kang SP, Metges JP; KEYNOTE-181 Investigators. Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer. J Clin Oncol. 2020 Dec 10;38(35):4138-4148. doi: 10.1200/JCO.20.01888. Epub 2020 Oct 7. — View Citation

Koom WS, Kim TH, Shin KH, Pyo HR, Kim JY, Kim DY, Yoon M, Park SY, Lee DH, Ryu JS, Jung YS, Lee SH, Cho KH. SMART (simultaneous modulated accelerated radiotherapy) for locally advanced nasopharyngeal carcinomas. Head Neck. 2008 Feb;30(2):159-69. doi: 10.1002/hed.20667. — View Citation

Ma JB, Wei L, Chen EC, Qin G, Song YP, Chen XM, Hao CG. Moderately hypofractionated conformal radiation treatment of thoracic esophageal carcinoma. Asian Pac J Cancer Prev. 2012;13(8):4163-7. doi: 10.7314/apjcp.2012.13.8.4163. — 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

Song YP, Ma JB, Hu LK, Zhou W, Chen EC, Zhang W. Phase I/II study of hypofractioned radiation with three-dimensional conformal radiotherapy for clinical T3-4N0-1M0 stage esophageal carcinoma. Technol Cancer Res Treat. 2011 Feb;10(1):25-30. doi: 10.7785/tcrt.2012.500176. — View Citation

Welsh J, Palmer MB, Ajani JA, Liao Z, Swisher SG, Hofstetter WL, Allen PK, Settle SH, Gomez D, Likhacheva A, Cox JD, Komaki R. Esophageal cancer dose escalation using a simultaneous integrated boost technique. Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):468-74. doi: 10.1016/j.ijrobp.2010.10.023. Epub 2010 Dec 1. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression-free survival rate		18-month
Secondary	overall survival rate		18-month
Secondary	Clinical response rate	the percentage of patients who had partial remission or complete remission after therapy	2 months after radiotherapy
Secondary	the rate of grade 3 or 4 toxicities according to CTCAE4.0	the percentage of patients who develop grade 3 or 4 toxicities	1 year after therapy
Secondary	distant metastasis-free survival		18-month
Secondary	locoregional recurrence-free survival		18-month
Secondary	Quality of life assessed by QLQ-C30		12 months