Neoadjuvant Chemoradiotherapy Combined With Perioperative Toripalimab in Locally Advanced Esophageal Cancer

NCT ID: NCT04437212

Last Updated: 2020-06-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-01
• Study Completion Date: 2023-12-31

Brief Summary

Neoadjuvant chemoradiotherapy (CRT) followed by surgery has become the standard treatment option for locally advanced esophageal squamous cell cancer (ESCC). However, only 20% to 40% of patients can achieve pathologic complete response (pCR) after neoadjuvant CRT with favorable prognosis and about 10% of patients have disease progression after chemoradiotherapy. How to improve the the efficacy of neoadjuvant therapy is an important clinical problem to be solved.

Immunotherapy targeting the PD-1/PD-L1 checkpoints has demonstrated promising activity in advanced EC especially in ESCC. In Keynote181 study, for patients with metastatic esophageal squamous cell carcinoma, regardless of PD-L1 expression, pembrolizumab significantly improved overall survival compared with chemotherapy. However, the efficacy and safety of immunotherapy therapy in surgery-based multidisciplinary treatment of local advanced esophageal cancer still need a lot of clinical studies to further confirm.

The aim of this study was to evaluate the efficacy and safety of the neoadjuvant chemoradiotherapy combined with perioperative toripalimab in patients with locally advanced esophageal squamous cell cancer.

Conditions

Advanced Esophageal Squamous Cell Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Toripalimab Group

All patients will receive radiation therapy scheme: 41.4Gy in 23 fractions over 5 weeks, concurrently with 5 cycles of paclitaxel/cisplatin (paclitaxel 45mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22,29 and 2 cycles of toripalimab 240 mg every 3 weeks after chemoradiotherapy. Esophagectomy is performed 6-8 weeks after CRT completion and after operation patients received 4 cycles of toripalimab 240 mg every 3 weeks for adjuvant treatment.

Group Type: EXPERIMENTAL

Toripalimab

Intervention Type: DRUG

Patients received toripalimab 240mg every 3 weeks 1-7 days after neoadjuvant chemoradiotherapy for 2 cycles before operation and 28-42 days after operation for 4 cycles.

Interventions

Toripalimab

Patients received toripalimab 240mg every 3 weeks 1-7 days after neoadjuvant chemoradiotherapy for 2 cycles before operation and 28-42 days after operation for 4 cycles.

Intervention Type: DRUG

Other Intervention Names

JS-001

Eligibility Criteria

Inclusion Criteria

• Aged 18 to 75 years old of either gender
• Patients with histopathological confirmed resectable thoracic esophageal squamous cell carcinoma who are anti-tumor treatment-naive;
• Clinical stage of T1-4aN1-2M0 or T3-4aN0M0 according to the 8th edition of the UICC staging system;
• ECOG PS score of 0-1;
• The indexes of hematology, biochemistry and organ function meet the following requirements: a. white blood cell count (WBC) ≥ 3.0×109/L；b. neutrophil count (ANC) ≥ 1.5×109/L; c. platelets ≥ 85×109/L; d. hemoglobin ≥ 9g/dL; e. total bilirubin ≤ 14.4µmol/L; f. ALT ≤ 75U/L; g. serum creatinine ≤ 104µmol/L and creatinine clearance rate >60 mL/min;
• Women of childbearing age must undergo a pregnancy test within 7 days before enrolling in the treatment, and those who are negative can be enrolled. Patients of childbearing age and their sexual partners agree to use reliable methods of contraception before entering the study, during the study, and at least 180 days after the end of the study;
• Ability to understand the study and sign informed consent.

Exclusion Criteria

• Patients with active infection within 2 weeks before the first use of the study drug or need to be treated with oral or intravenous antibiotics;
• A history of interstitial lung disease or non-infectious pneumonia;
• Patients whose clinician judges surgery as the first choice for the best treatment;
• A history of autoimmune diseases or abnormal immune system ;
• Patients who cannot tolerate chemoradiotherapy or surgery due to severe cardiac, lung dysfunction。
• Patients diagnosed with any other malignant tumor within 5 years before enrollment, except for malignant tumors with low risk of recurrence and risk of death, such as fully treated basal cell or squamous cell skin and carcinoma in situ of the cervix;
• Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of Toripalimab, and the chemotherapeutic drugs paclitaxel or cisplatin;
• 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;
• Women during pregnancy or lactation;
• Other situations not suitable for enrollment.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

RenJi Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xiumei Ma, doctor

Role: PRINCIPAL_INVESTIGATOR

RenJi Hospital

Locations

Renji Hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xiumei Ma, doctor

Role: CONTACT

sallyma@hotmail.com

86-21-68683624

Facility Contacts

Xiumei Ma, doctor

Role: primary

sallyma@hotmail.com

86-21-68383624

References

Xu X, Sun Z, Liu Q, Zhang Y, Shen L, Zhang C, Lin H, Hu B, Rong L, Chen H, Wang X, Zhao X, Bai YR, Ye Q, Ma X. Neoadjuvant chemoradiotherapy combined with sequential perioperative toripalimab in locally advanced esophageal squamous cell cancer. J Immunother Cancer. 2024 Mar 7;12(3):e008631. doi: 10.1136/jitc-2023-008631.

Reference Type: DERIVED

PMID: 38458635 (View on PubMed)

Other Identifiers

Renji-KY2019-174

Identifier Type: -

Identifier Source: org_study_id