Combination of Toripalimab and Neoadjuvant Chemoradiotherapy in Esophageal Cancer

NCT ID: NCT04006041

Last Updated: 2019-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-25

Study Completion Date

2020-12-31

Brief Summary

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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).

Detailed Description

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Conditions

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Esophageal Squamous Cell Carcinoma by AJCC V8 Stage Resectable Esophageal Cancer

Keywords

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Esophageal squamous cell carcinoma Neoadjuvant chemoradiotherapy Toripalimab Pathologic complete response

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Toripalimab group

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.

Group Type EXPERIMENTAL

Toripalimab

Intervention Type DRUG

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

Paclitaxel/cisplatin

Intervention Type 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.

Intensity-modulated radiotherapy

Intervention Type RADIATION

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

Esophagectomy

Intervention Type PROCEDURE

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

Interventions

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Toripalimab

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

Intervention Type DRUG

Paclitaxel/cisplatin

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

Intervention Type DRUG

Intensity-modulated radiotherapy

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

Intervention Type RADIATION

Esophagectomy

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

Intervention Type PROCEDURE

Other Intervention Names

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JS-001 TP IMRT

Eligibility Criteria

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Inclusion Criteria

1. 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;
2. Patients who are anti-tumor treatment-naive;
3. Estimated life expectancy \>6 months
4. Aged 18 to 70 years old of either gender
5. 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;
6. PS score of 0-1;
7. Ability to understand the study and sign informed consent.

Exclusion Criteria

1. Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.);
2. Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of Toripalimab, and the chemotherapeutic drugs paclitaxel or cisplatin;
3. Patients who have a preexisting or coexisting bleeding disorder;
4. Other uncontrollable inoperable patients;
5. Female patients who are pregnant or lactating;
6. Inability to provide informed consent due to psychological, familial, social and other factors;
7. Presence of CTC grade ≥ 3 peripheral neuropathy;
8. A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer
9. A history of diabetes for more than 10 years and poorly controlled blood glucose levels;
10. Patients who cannot tolerate chemoradiotherapy or surgery due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia.
11. 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;
12. A history of interstitial lung disease or non-infectious pneumonia;
13. 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;
14. 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).
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Jianhua Fu

OTHER

Sponsor Role lead

Responsible Party

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Jianhua Fu

Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Jianhua Fu, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

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Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Mian Xi, MD

Role: CONTACT

Phone: 86-20-87343385

Email: [email protected]

Hong Yang, MD

Role: CONTACT

Phone: 86-20-87343093

Email: [email protected]

Facility Contacts

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Mian Xi, MD

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 30089078 (View on PubMed)

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.

Reference Type RESULT
PMID: 28317872 (View on PubMed)

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.

Reference Type RESULT
PMID: 30642373 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39235488 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37560259 (View on PubMed)

Other Identifiers

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TORINEOEC

Identifier Type: -

Identifier Source: org_study_id