Combination of Toripalimab and Neoadjuvant Chemoradiotherapy in Esophageal Cancer

NCT04006041 | Unknown Phase 2 DMC

• 1 other identifier: TORINEOEC
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Neoadjuvant chemoradiotherapy (CRT) followed by surgery has become the standard treatment option for locally advanced esophageal cancer (EC). However, only 20% to 40% of EC patients can achieve pathologic complete response (pCR) after neoadjuvant CRT with favorable prognosis. Immunotherapy targeting the PD-1/PD-L1 checkpoints has demonstrated promising activity in advanced EC. The aim of this study was to evaluate the efficacy and safety of the combination of toripalimab (an anti-PD-1 antibody) combined with neoadjuvant CRT in locally advanced esophageal squamous cell carcinoma (ESCC).

Conditions

Esophageal Squamous Cell Carcinoma by AJCC V8 Stage; Resectable Esophageal Cancer

Keywords

Esophageal squamous cell carcinoma; Neoadjuvant chemoradiotherapy; Toripalimab; Pathologic complete response

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response rate

  The rate of pathologic complete response rate after neoadjuvant chemoradiotherapy.

  Three working days after surgery

Secondary Outcomes (6)

• 2-year overall survival

  From date of randomization until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 24 months

• 2-year disease-free survival

  From date of surgery until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months.

• Incidence of Treatment-related Adverse Events as Assessed by CTCAE v4.0

  From the enrollment to the date of surgery

• R0 resection rate

  Three working days after surgery

• Perioperative complication rate

  From date of surgery to 30 days later

Study Arms (1)

Toripalimab group

EXPERIMENTAL

All patients will receive standard fractionation radiation therapy (RT) scheme: 44Gy in 20 fractions over 4 weeks, concurrently with 4 cycles of paclitaxel/cisplatin (paclitaxel 50mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22 and 2 cycles of toripalimab 240 mg on days 1, 22. Esophagectomy is performed 6-8 weeks after CRT completion.

Drug: Toripalimab; Drug: Paclitaxel/cisplatin; Radiation: Intensity-modulated radiotherapy; Procedure: Esophagectomy

Interventions

Toripalimab DRUG

Patients received toripalimab 240 mg IVDRIP on days 1 and 22 during neoadjuvant radiotherapy.

Also known as: JS-001

Toripalimab group

Paclitaxel/cisplatin DRUG

Patients received 4 cycles of paclitaxel/cisplatin (paclitaxel 50mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22 during neoadjuvant radiotherapy.

Also known as: TP

Toripalimab group

Intensity-modulated radiotherapy RADIATION

All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is 44 Gy in 20 fractions over 4 weeks.

Also known as: IMRT

Toripalimab group

Esophagectomy PROCEDURE

A transthoracic (Ivor-Lewis) esophagectomy is performed 6-8 weeks after CRT completion.

Toripalimab group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A histopathological diagnosis of resectable thoracic esophageal squamous cell carcinoma with a pre-treatment clinical stage of T1-4aN1-3M0 or T3-4aN0M0 according to the 8th edition of the UICC staging system;
• Patients who are anti-tumor treatment-naive;
• Estimated life expectancy \>6 months
• Aged 18 to 70 years old of either gender
• The function of important organs meets the following requirements: a. white blood cell count (WBC) ≥ 4.0×109/L, absolute neutrophil count (ANC) ≥ 1.5×109/L; b. platelets ≥ 100×109/L; c. hemoglobin ≥ 9g/dL; d. serum albumin ≥ 2.8g/dL; e. total bilirubin ≤ 1.5×ULN, ALT, AST and/or AKP ≤ 2.5×ULN; f. serum creatinine ≤ 1.5×ULN or creatinine clearance rate \>60 mL/min;
• PS score of 0-1;
• Ability to understand the study and sign informed consent.

You may not qualify if:

• Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.);
• Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of Toripalimab, and the chemotherapeutic drugs paclitaxel or cisplatin;
• Patients who have a preexisting or coexisting bleeding disorder;
• Other uncontrollable inoperable patients;
• Female patients who are pregnant or lactating;
• Inability to provide informed consent due to psychological, familial, social and other factors;
• Presence of CTC grade ≥ 3 peripheral neuropathy;
• A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer
• A history of diabetes for more than 10 years and poorly controlled blood glucose levels;
• Patients who cannot tolerate chemoradiotherapy or surgery due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia.
• Active autoimmune diseases, a history of autoimmune diseases (including but not limited to these diseases or syndromes, such as colitis, hepatitis, hyperthyroidism), a history of immunodeficiency (including a positive HIV test result), or other acquired or congenital immunodeficiency diseases, a history of organ transplantation or allogeneic bone marrow transplantation;
• A history of interstitial lung disease or non-infectious pneumonia;
• A history of active pulmonary tuberculosis infection within 1 year or a history of active pulmonary tuberculosis infection more than 1 year ago but without formal anti-tuberculosis treatment;
• Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit of the assay).

Sponsors & Collaborators

• Jianhua Fu: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (5)

• Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Chen Z, Yang H, Wang J, Pang Q, Zheng X, Yang H, Li T, Lordick F, D'Journo XB, Cerfolio RJ, Korst RJ, Novoa NM, Swanson SJ, Brunelli A, Ismail M, Fernando HC, Zhang X, Li Q, Wang G, Chen B, Mao T, Kong M, Guo X, Lin T, Liu M, Fu J; AME Thoracic Surgery Collaborative Group. Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial. J Clin Oncol. 2018 Sep 20;36(27):2796-2803. doi: 10.1200/JCO.2018.79.1483. Epub 2018 Aug 8.

  PMID: 30089078 BACKGROUND

• Fu J, Wang F, Dong LH, Zhang J, Deng CL, Wang XL, Xie XY, Zhang J, Deng RX, Zhang LB, Wu H, Feng H, Chen B, Song HF. Preclinical evaluation of the efficacy, pharmacokinetics and immunogenicity of JS-001, a programmed cell death protein-1 (PD-1) monoclonal antibody. Acta Pharmacol Sin. 2017 May;38(5):710-718. doi: 10.1038/aps.2016.161. Epub 2017 Mar 20.

  PMID: 28317872 RESULT

• Tang B, Yan X, Sheng X, Si L, Cui C, Kong Y, Mao L, Lian B, Bai X, Wang X, Li S, Zhou L, Yu J, Dai J, Wang K, Hu J, Dong L, Song H, Wu H, Feng H, Yao S, Chi Z, Guo J. Safety and clinical activity with an anti-PD-1 antibody JS001 in advanced melanoma or urologic cancer patients. J Hematol Oncol. 2019 Jan 14;12(1):7. doi: 10.1186/s13045-018-0693-2.

  PMID: 30642373 RESULT

• Mai Z, Kongjia L, Wang X, Xie X, Pang L, Yang H, Wen J, Fu J. Impaired TGF-beta signaling via AHNAK family mutations elicits an esophageal cancer subtype with sensitivities to genotoxic therapy and immunotherapy. Cancer Immunol Immunother. 2024 Sep 5;73(11):225. doi: 10.1007/s00262-024-03798-z.

  PMID: 39235488 DERIVED

• Chen R, Liu Q, Li Q, Zhu Y, Zhao L, Liu S, Chen B, Liu M, Hu Y, Lin T, Li J, Chen J, Lv Y, Fu J, Xi M, Yang H. A phase II clinical trial of toripalimab combined with neoadjuvant chemoradiotherapy in locally advanced esophageal squamous cell carcinoma (NEOCRTEC1901). EClinicalMedicine. 2023 Jul 26;62:102118. doi: 10.1016/j.eclinm.2023.102118. eCollection 2023 Aug.

  PMID: 37560259 DERIVED

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma; Pathologic Complete Response

Interventions

toripalimab; TP protocol; Radiotherapy, Intensity-Modulated; Esophagectomy

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; Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Digestive System Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Jianhua Fu, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mian Xi, MD

CONTACT

86-20-87343385; ximian@sysucc.org.cn

Hong Yang, MD

CONTACT

86-20-87343093; yanghong@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 26, 2019
• First Posted: July 2, 2019
• Study Start: June 25, 2019
• Primary Completion: June 30, 2020
• Study Completion: December 31, 2020
• Last Updated: December 26, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)