Combination of Toripalimab and Neoadjuvant Chemoradiotherapy in Esophageal Cancer

Phase 2

• Conditions: Resectable Esophageal Cancer; Esophageal Squamous Cell Carcinoma by AJCC V8 Stage
• Interventions: Drug: Toripalimab; Drug: Paclitaxel/cisplatin; Radiation: Intensity-modulated radiotherapy; Procedure: Esophagectomy

• Registration Number: NCT04006041
• Lead Sponsor: Jianhua Fu

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2019-06-25
• Study First Submitted: 2019-06-26
• Study First Submitted QC: 2019-06-30
• Study First Posted: 2019-07-02
• Status Verified: 2019-12
• Last Update Submitted: 2019-12-22
• Last Update Posted: 2019-12-26
• Primary Completion: 2020-06-30
• Study Completion: 2020-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 44

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Toripalimab group	Paclitaxel/cisplatin	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.
Toripalimab group	Esophagectomy	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.
Toripalimab group	Intensity-modulated radiotherapy	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.
Toripalimab group	Toripalimab	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.

Primary Outcome Measures

Name	Time	Method
Pathologic complete response rate	Three working days after surgery	The rate of pathologic complete response rate after neoadjuvant chemoradiotherapy.

Secondary Outcome Measures

Name	Time	Method
Perioperative complication rate	From date of surgery to 30 days later	The perioperative complication rate of esophagectomy
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	The 2-year overall survival of the whole group
R0 resection rate	Three working days after surgery	The R0 resection rate of esophagectomy
Incidence of Treatment-related Adverse Events as Assessed by CTCAE v4.0	From the enrollment to the date of surgery	The neoadjuvant treatment-related adverse events
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.	The 2-year disease-free survival of the whole group
Perioperative mortality	From date of surgery to 30 days later	The perioperative mortality of esophagectomy

Trial Locations

Locations (1)

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China