Combination of Toripalimab and Neoadjuvant Chemoradiotherapy in Esophageal Cancer

Resectable Esophageal Cancer Clinical Trial

Official title:

A Phase II Trial of Combination of Toripalimab and Neoadjuvant Chemoradiotherapy in Esophageal Squamous Cell Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04006041
• Other study ID #: TORINEOEC
• Status: Recruiting
• Phase: Phase 2
• Start date: June 25, 2019
• Est. completion date: December 31, 2020

Study information

• Verified date: December 2019
• Source: Sun Yat-sen University
• Contact: Mian Xi, MD
• Phone: 86-20-87343385
• Email: ximian[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: December 31, 2020
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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).

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Neoplasms
• Esophageal Squamous Cell Carcinoma
• Esophageal Squamous Cell Carcinoma by AJCC V8 Stage
• Resectable Esophageal Cancer

Intervention

Drug:
• Toripalimab
Patients received toripalimab 240 mg IVDRIP on days 1 and 22 during neoadjuvant radiotherapy.
• 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.

Radiation:
• 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.

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Jianhua Fu

Country where clinical trial is conducted

China, 

References & Publications (3)

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 — View Citation

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 ur — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic complete response rate	The rate of pathologic complete response rate after neoadjuvant chemoradiotherapy.	Three working days after surgery
Secondary	2-year overall survival	The 2-year overall survival of the whole group	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
Secondary	2-year disease-free survival	The 2-year disease-free survival of the whole group	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.
Secondary	Incidence of Treatment-related Adverse Events as Assessed by CTCAE v4.0	The neoadjuvant treatment-related adverse events	From the enrollment to the date of surgery
Secondary	R0 resection rate	The R0 resection rate of esophagectomy	Three working days after surgery
Secondary	Perioperative complication rate	The perioperative complication rate of esophagectomy	From date of surgery to 30 days later
Secondary	Perioperative mortality	The perioperative mortality of esophagectomy	From date of surgery to 30 days later