Toripalimab With Paclitaxel and Cisplatin as Neoadjuvant Treatment for Esophageal Squamous Cell Carcinoma
Primary Purpose
Esophageal Squamous Cell Cancer
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Toripalimab
Paclitaxel
Cisplatin
Sponsored by
About this trial
This is an interventional treatment trial for Esophageal Squamous Cell Cancer
Eligibility Criteria
Inclusion Criteria:
- Age: 18-70 years old, both gender.
- Histopathologically confirmed esophageal squamous cell carcinoma.
- No previous chemotherapy, radiotherapy, traditional Chinese medicine and other anti-tumor treatments.
- Imaging (CT or MR) or ultrasound endoscopy confirmed local advanced resectable lesions ( AJCC 8th edition standard, stage 3N0M0 or T1-4aN+M0).
- The ECOG performance status score of 0-1.
Normal functionof all major organs, that is:
Hemoglobin (Hb) ≥ 100g/L,
- Neutrophils (ANC) ≥ 1.5×109/L, ③ Platelet count (PLT) ≥100×109/L, ④ Prothrombin time (PT) and partial prothrombin time (PTT) ≤ 1.5×upper limit of normal (ULN). (For the use of a stable dose of anticoagulant therapy such as low molecular weight heparin or warfarin, if the INR is within the expected therapeutic range of anticoagulants, patient could be screened); ⑤ Serum creatinine (Cr) ≤ 1.5 ×ULN, or 24-hour creatinine clearance rate >60mL/min(Cockcroft-Gault); ⑥ Total blood bilirubin (TB) ≤ 1.5ULN; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5×ULN; albumin (ALB) ≥ 30g/L.
- The cardiac function is basically normal, the left ventricular ejection fraction is ≥50%, and the blood pressure is under controlled within 140/90 mmHg before enrollment.
- Pulmonary function is basically normal, without moderate to severe obstructive and diffuse dysfunction.
- Be able to provide tissue samples for biomarkers analysis, such as PD-L1 expression.
- Women of childbearing age must have taken reliable contraceptive measures or undergo a pregnancy test (serum) within 7 days before enrollment, and the result is negative, and are willing to use appropriate methods of contraception. For men, they must agree to use appropriate methods of contraception or have been surgically sterilized during the trial period and within 8 weeks after the last trial drug administration;
- Voluntarily sign an informed consent form (or signed by a legal representative) to prove that they understand the purpose of the research and the operations required by the research and are willing to participate in the research.
Exclusion Criteria:
- Adenocarcinoma, small cell carcinoma, and other non-squamous cell carcinoma types of esophageal cancer.
- Imaging examinations (CT or MRI) or endoscopic ultrasonography revealed early stage esophageal cancer, including: carcinoma in situ (Tis), lesions only invaded the mucosa layer or the muscularis propria without lymph node metastasis (T1-2N0).
- Imaging examinations (CT or MRI) revealed unresectable disease including invasion of vertebral body, aorta, and organs (T4b), or with distant metastases such as lungs, liver, bones and other organ metastases (M1) ;
- Imaging (esophagography, CT or MR) examination within 4 weeks before enrollment revealed esophageal mediastinal fistula or esophagotracheal fistula.
- Gastrointestinal bleeding such as hematemesis or melena within 4 weeks before the first dose of treatment.
- Allergic to PD-1 antibodies, paclitaxel, or cisplatin.
- Receiving previous anti-tumor treatments such as chemotherapy, radiotherapy, molecular targeted therapy, or Chinese medicine treatment within 4 weeks before enrollment.
- Receiving corticosteroids (>10 mg prednisone or equivalent dose per day) or other immunosuppressive therapy within 2 weeks before enrollment, except for those who use corticosteroids to prevent allergies, nausea, and vomiting.
- Received live vaccines within 4 weeks before the first dose of treatment.
- Receiving major surgery or suffered severe trauma within 4 weeks before the first dose of treatment.
- Complicated with active autoimmune diseases, or history of autoimmune diseases (such as interstitial pneumonia, colitis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but Not limited to these diseases or syndromes). Except: vitiligo, cured childhood asthma/allergic adults without any intervention, autoimmune-mediated hypothyroidism treated with a stable dose of thyroid replacement hormone, and type I diabetes with a stable dose of insulin.
- A history of immunodeficiency, including HIV positive, acquired or congenital immunodeficiency diseases, organ transplantation, or bone marrow transplantation.
- With clinical symptoms of cardiovascular diseases which were not well controlled, including but not limited to: heart failure above NYHA II; unstable angina; myocardial infarction within 1 year; clinically significant supraventricular or ventricular arrhythmia and is still uncontrolled without clinical intervention or clinical intervention;
- Severe infections (CTC AE> Grade 2) occurred within 4 weeks before the first dose of treatment, such as severe pneumonia, bacteremia, infectious comorbidities that require hospitalization, etc.; baseline chest imaging examinations suggest the presence of active lungs Inflammation; having symptoms and signs of infection or taken oral or intravenous antibiotic treatment within 2 weeks before the first dose of treatment except for prophylactic use of antibiotics.
- A history of interstitial lung disease and a history of non-infectious pneumonia.
- With active pulmonary tuberculosis infection identified by medical history or CT examination, or a history of active pulmonary tuberculosis infection within 1 year before enrollment.
- Active hepatitis B (quantity of HBV DNA ≥100 IU/mL), or hepatitis C (hepatitis C antibody is positive, and HCV-RNA is higher than the lower limit of the analytical method) infection.
- Complicated with chronic nephritis, or urine routine test indicates urine protein ≥ ++, or 24-hour urine protein ≥ 1.0 g.
- Abnormal blood coagulation function (INR or PT or PTT> 1.5 ULN), potential risk of bleeding, or receiving thrombolysis or anticoagulation therapy;
- With other malignant tumor diagnosed within 5 years before the first dose of treatment. Exclude malignant tumors with low risk of metastasis and death, such as fully treated basal cell or squamous cell skin cancer or cervical carcinoma in situ.
- Women who are pregnant or breastfeeding.
- According to the researcher's judgment, there are other factors that may lead to forced termination. Such as suffering from other serious diseases (including mental illness) requiring combined treatment, significant abnormal laboratory test values, or family or social factors, etc., may affect the safety of subjects or the collection of experimental data.
Sites / Locations
- Beijing Cancer Hospital / Peking University Cancer HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
TPC treatment
Arm Description
Neoadjuvant treatment of toripalimab, paclitaxel and cisplatin
Outcomes
Primary Outcome Measures
Pathologic complete response rate
The rate of pathologic complete response rate after neoadjuvant therapy.
Secondary Outcome Measures
Objective Response Rate
The percentage of patients having a complete response or a partial response to protocol treatment. Objective response will be measured by RECIST 1.1.
R0 resection rate
The R0 resection rate of esophagectomy
Major pathologic response rate
The percentage of subjects with ≤10% survival tumor cells in the resected specimens after neoadjuvant therapy accounted for all subjects who received surgical treatment.
Disease-free survival
The time from enrollment to recurrence of tumor or death.
Overall survival
The length of time from enrollment until the time of death
Adverse events
The incidence of adverse events and the incidence of severe adverse events( grade 3-4) .
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04804696
Brief Title
Toripalimab With Paclitaxel and Cisplatin as Neoadjuvant Treatment for Esophageal Squamous Cell Carcinoma
Official Title
Toripalimab With Paclitaxel and Cisplatin as Neoadjuvant Treatment for Esophageal Squamous Cell Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 10, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Neoadjuvant chemoradiotherapy or chemotherapy followed by surgery is the standard treatment for local advanced esophageal cancer (EC). It had been demonstrated that patients who achieve pathologic complete response (pCR) after neoadjuvant treatment had better prognosis. However, the pCR rate were about only 5-10% in neoadjuvant chemotherapy and 20-40% in neoadjuvant concurrent chemoradiotherapy.
PD-1 antibody based immunotherapy alone as second-line treatment or combined with chemotherapy as first-line treatment had been proved that could prolong overall survival of EC patients. And a recent phase 3 clinical trial CheckMate 577 reported that, as adjuvant treatment, nivolumab could improve disease-free survival in EC and esophageal-gastric junction cancer.
The aim of this study was to evaluate the efficacy and safety of toripalimab, an anti-PD-1 antibody, combined with paclitaxel and cisplatin as neoadjuvant treatment in local advanced esophageal squamous cell carcinoma (ESCC). We hope this combining treatment would increase the pCR rate of neoadjuvant chemotherapy and improve survival of patients, and at the menatime avoid the adverse events of neoadjuvant radiotherapy. This study will provide valuable information for further clinical trials of both Toripalimab and other immune checkpoint inhibition agents in treatment of esophageal cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
53 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
TPC treatment
Arm Type
Experimental
Arm Description
Neoadjuvant treatment of toripalimab, paclitaxel and cisplatin
Intervention Type
Drug
Intervention Name(s)
Toripalimab
Other Intervention Name(s)
JS001, TAB001
Intervention Description
Patients received toripalimab 240 mg I.V. drip on days 1 and 22.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
Patients received paclitaxel of 175mg/m2 I.V. drip on days 1 and 22.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Patients received cisplatin of 70mg/m2 I.V. drip on days 1 and 22.
Primary Outcome Measure Information:
Title
Pathologic complete response rate
Description
The rate of pathologic complete response rate after neoadjuvant therapy.
Time Frame
Three weeks after surgery of last enrolled subject. Estimate up to 2 years
Secondary Outcome Measure Information:
Title
Objective Response Rate
Description
The percentage of patients having a complete response or a partial response to protocol treatment. Objective response will be measured by RECIST 1.1.
Time Frame
One month after 2 cycles' treatment of last enrolled subject. Estimate up to 2 years
Title
R0 resection rate
Description
The R0 resection rate of esophagectomy
Time Frame
Three weeks after surgery of last enrolled subject. Estimate up to 2 years
Title
Major pathologic response rate
Description
The percentage of subjects with ≤10% survival tumor cells in the resected specimens after neoadjuvant therapy accounted for all subjects who received surgical treatment.
Time Frame
Three weeks after surgery of last enrolled subject. Estimate up to 2 years.
Title
Disease-free survival
Description
The time from enrollment to recurrence of tumor or death.
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. Estimate up to three years.
Title
Overall survival
Description
The length of time from enrollment until the time of death
Time Frame
From enrollment to death of patients. Estimate up to 5 years.
Title
Adverse events
Description
The incidence of adverse events and the incidence of severe adverse events( grade 3-4) .
Time Frame
From enrollment to 60 days after the end protocol treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age: 18-70 years old, both gender.
Histopathologically confirmed esophageal squamous cell carcinoma.
No previous chemotherapy, radiotherapy, traditional Chinese medicine and other anti-tumor treatments.
Imaging (CT or MR) or ultrasound endoscopy confirmed local advanced resectable lesions ( AJCC 8th edition standard, stage 3N0M0 or T1-4aN+M0).
The ECOG performance status score of 0-1.
Normal functionof all major organs, that is:
Hemoglobin (Hb) ≥ 100g/L,
Neutrophils (ANC) ≥ 1.5×109/L, ③ Platelet count (PLT) ≥100×109/L, ④ Prothrombin time (PT) and partial prothrombin time (PTT) ≤ 1.5×upper limit of normal (ULN). (For the use of a stable dose of anticoagulant therapy such as low molecular weight heparin or warfarin, if the INR is within the expected therapeutic range of anticoagulants, patient could be screened); ⑤ Serum creatinine (Cr) ≤ 1.5 ×ULN, or 24-hour creatinine clearance rate >60mL/min(Cockcroft-Gault); ⑥ Total blood bilirubin (TB) ≤ 1.5ULN; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5×ULN; albumin (ALB) ≥ 30g/L.
The cardiac function is basically normal, the left ventricular ejection fraction is ≥50%, and the blood pressure is under controlled within 140/90 mmHg before enrollment.
Pulmonary function is basically normal, without moderate to severe obstructive and diffuse dysfunction.
Be able to provide tissue samples for biomarkers analysis, such as PD-L1 expression.
Women of childbearing age must have taken reliable contraceptive measures or undergo a pregnancy test (serum) within 7 days before enrollment, and the result is negative, and are willing to use appropriate methods of contraception. For men, they must agree to use appropriate methods of contraception or have been surgically sterilized during the trial period and within 8 weeks after the last trial drug administration;
Voluntarily sign an informed consent form (or signed by a legal representative) to prove that they understand the purpose of the research and the operations required by the research and are willing to participate in the research.
Exclusion Criteria:
Adenocarcinoma, small cell carcinoma, and other non-squamous cell carcinoma types of esophageal cancer.
Imaging examinations (CT or MRI) or endoscopic ultrasonography revealed early stage esophageal cancer, including: carcinoma in situ (Tis), lesions only invaded the mucosa layer or the muscularis propria without lymph node metastasis (T1-2N0).
Imaging examinations (CT or MRI) revealed unresectable disease including invasion of vertebral body, aorta, and organs (T4b), or with distant metastases such as lungs, liver, bones and other organ metastases (M1) ;
Imaging (esophagography, CT or MR) examination within 4 weeks before enrollment revealed esophageal mediastinal fistula or esophagotracheal fistula.
Gastrointestinal bleeding such as hematemesis or melena within 4 weeks before the first dose of treatment.
Allergic to PD-1 antibodies, paclitaxel, or cisplatin.
Receiving previous anti-tumor treatments such as chemotherapy, radiotherapy, molecular targeted therapy, or Chinese medicine treatment within 4 weeks before enrollment.
Receiving corticosteroids (>10 mg prednisone or equivalent dose per day) or other immunosuppressive therapy within 2 weeks before enrollment, except for those who use corticosteroids to prevent allergies, nausea, and vomiting.
Received live vaccines within 4 weeks before the first dose of treatment.
Receiving major surgery or suffered severe trauma within 4 weeks before the first dose of treatment.
Complicated with active autoimmune diseases, or history of autoimmune diseases (such as interstitial pneumonia, colitis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but Not limited to these diseases or syndromes). Except: vitiligo, cured childhood asthma/allergic adults without any intervention, autoimmune-mediated hypothyroidism treated with a stable dose of thyroid replacement hormone, and type I diabetes with a stable dose of insulin.
A history of immunodeficiency, including HIV positive, acquired or congenital immunodeficiency diseases, organ transplantation, or bone marrow transplantation.
With clinical symptoms of cardiovascular diseases which were not well controlled, including but not limited to: heart failure above NYHA II; unstable angina; myocardial infarction within 1 year; clinically significant supraventricular or ventricular arrhythmia and is still uncontrolled without clinical intervention or clinical intervention;
Severe infections (CTC AE> Grade 2) occurred within 4 weeks before the first dose of treatment, such as severe pneumonia, bacteremia, infectious comorbidities that require hospitalization, etc.; baseline chest imaging examinations suggest the presence of active lungs Inflammation; having symptoms and signs of infection or taken oral or intravenous antibiotic treatment within 2 weeks before the first dose of treatment except for prophylactic use of antibiotics.
A history of interstitial lung disease and a history of non-infectious pneumonia.
With active pulmonary tuberculosis infection identified by medical history or CT examination, or a history of active pulmonary tuberculosis infection within 1 year before enrollment.
Active hepatitis B (quantity of HBV DNA ≥100 IU/mL), or hepatitis C (hepatitis C antibody is positive, and HCV-RNA is higher than the lower limit of the analytical method) infection.
Complicated with chronic nephritis, or urine routine test indicates urine protein ≥ ++, or 24-hour urine protein ≥ 1.0 g.
Abnormal blood coagulation function (INR or PT or PTT> 1.5 ULN), potential risk of bleeding, or receiving thrombolysis or anticoagulation therapy;
With other malignant tumor diagnosed within 5 years before the first dose of treatment. Exclude malignant tumors with low risk of metastasis and death, such as fully treated basal cell or squamous cell skin cancer or cervical carcinoma in situ.
Women who are pregnant or breastfeeding.
According to the researcher's judgment, there are other factors that may lead to forced termination. Such as suffering from other serious diseases (including mental illness) requiring combined treatment, significant abnormal laboratory test values, or family or social factors, etc., may affect the safety of subjects or the collection of experimental data.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jun Jia, M.D.
Phone
+86-10-88196956
Email
bdzlvip@163.com
Facility Information:
Facility Name
Beijing Cancer Hospital / Peking University Cancer Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jun Jia, M.D.
Phone
+86-1088196956
Email
bdzlvip@163.com
First Name & Middle Initial & Last Name & Degree
Xiaodong Zhang, M.D.
Phone
+86-10-88196957
Email
bdzlvip@163.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Toripalimab With Paclitaxel and Cisplatin as Neoadjuvant Treatment for Esophageal Squamous Cell Carcinoma
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