Back to resultsNeoadjuvant Chemoradiotherapy Combined With Perioperative Toripalimab in Locally Advanced Esophageal Cancer
Primary Purpose
Advanced Esophageal Squamous Cell Cancer
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Toripalimab
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Esophageal Squamous Cell Cancer
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.
Sites / Locations
- Renji HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Toripalimab Group
Arm Description
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.
Outcomes
Primary Outcome Measures
Major Pathological Response Rate (MPR)
No more than 10% of tumor cells were found in neoadjuvant surgical specimens.
Secondary Outcome Measures
2-year disease-free survival
2-year overall survival
Incidence of Treatment-related Adverse Events as Assessed by CTCAE v5.0
Perioperative complication rate
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04437212
Brief Title
Neoadjuvant Chemoradiotherapy Combined With Perioperative Toripalimab in Locally Advanced Esophageal Cancer
Official Title
A Phase II Prospective, Open-label Clinical Trial of Neoadjuvant Chemoradiotherapy Combined With Perioperative Toripalimab in Patients With Locally Advanced Esophageal Squamous Cell Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2020 (Anticipated)
Primary Completion Date
December 31, 2021 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
RenJi Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Esophageal Squamous Cell Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Toripalimab Group
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Toripalimab
Other Intervention Name(s)
JS-001
Intervention Description
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.
Primary Outcome Measure Information:
Title
Major Pathological Response Rate (MPR)
Description
No more than 10% of tumor cells were found in neoadjuvant surgical specimens.
Time Frame
From date of surgery to 14 days later
Secondary Outcome Measure Information:
Title
2-year disease-free survival
Time Frame
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.
Title
2-year overall survival
Time Frame
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
Title
Incidence of Treatment-related Adverse Events as Assessed by CTCAE v5.0
Time Frame
60 days after the end protocol treatment
Title
Perioperative complication rate
Time Frame
From date of surgery to 30 days later
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiumei Ma, doctor
Phone
86-21-68683624
Email
sallyma@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiumei Ma, doctor
Organizational Affiliation
RenJi Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Renji Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200127
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiumei Ma, doctor
Phone
86-21-68383624
Email
sallyma@hotmail.com
First Name & Middle Initial & Last Name & Degree
Xiumei Ma, doctor
12. IPD Sharing Statement
Learn more about this trial
Neoadjuvant Chemoradiotherapy Combined With Perioperative Toripalimab in Locally Advanced Esophageal Cancer
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