Locally Advanced Esophageal Squamous Cell Carcinoma
Conditions
Keywords
Esophageal squamous cell carcinoma, Neoadjuvant chemotherapy, Nivolumab, JCOG
Brief summary
The main purpose of this study is to evaluate the safety of the neoadjuvant therapy, nivolumab with CF (5-FU, CDDP) or nivolumab with DCF (5-FU, CDDP, DTX), for locally advanced esophageal carcinoma.
Interventions
Sponsors
Ono Pharmaceutical Co. Ltd
Fiverings Co., Ltd.
National Cancer Center, Japan
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Endoscopic biopsy of esophageal primary lesion histologically diagnosed as squamous cell carcinoma, adenosquamous carcinoma, or basal cell carcinoma 2. All esophageal cancer lesions are localized in the thoracic esophagus 3. Patients are classified as clinical stage T1N1-3M0 or T2-3N0-3M0 in the UICC-TNM classification 8th edition 4. The age is over 20 years old and under 75 on the enrollment date 5. PS 0-1 6. With or without measurable lesions 7. Patients who have no medical history of treatment for esophageal cancer 8. Patients who have no medical history of chemotherapy, radiotherapy, and endocrine therapy, including treatment for other types of cancer 9. The results of laboratory tests within 14 days before enrollment meet the inclusion criteria 10. Esophageal cancer radical surgery (R0) by open-chest surgery (or thoracoscopic surgery) and laparotomy (or laparoscopic surgery) is judged possible 11. Patients who have no complication or history of thyroid dysfunction 12. Patients who have no complication or history of autoimmune disease 13. Patients who don't have treatment with systemic corticosteroids (dose of 10mg/day over in prednisolone equivalent) or immunosuppressants within 14 days before enrollment 14. Patients who have no complication or history of pneumonitis or pulmonary fibrosis which had been diagnosed by imaging tests or physical examination 15. For females, who have agreed with contraception from start of investigational drug administration to 5 months after last dose of an investigational drug. For males who have agreed with contraception from start of investigational drug administration to 7 months after last dose of an investigational drug. 16. Obtained written informed consent from patients
Exclusion criteria
1. Patients who have active multiple cancers 2. Patients who have an infectious disease that is active and need the systemic treatment 3. Positive with HBs antigen, HCV-RNA or anti-HIV antibody, or anti-HTLV-1 antibody tests 4. Negative with HBs antigen test and positive with anti HBs antibody or anti HBc antibody tests, and positive with HBV-DNA quantitative test 5. Pregnant, suspected pregnant, or lactating 6. Patients who have Psycosis or psychiatric symptoms are judged inappropriate for participation in the trial 7. Patients who need the treatment with continued use of flucytosine, phenytoin, or warfarin potassium 8. Patients who have a medical history of allergy to iodine 9. Patients who have hypersensitivity to docetaxel, cisplatin, and drug-containing polysorbate 80 10. Patients who have a complication or a history of highly sensitive reactions to antibody formulations 11. Even if insulin or oral hypoglycemic agent is continued use, the result of HbA1c test is 6.5% or more in JDS or 6.9% or more in NGSP 12. Patients who have advanced pulmonary emphysema, which is observed by pulmonary function test or CT test 13. Patients who have uncontrollable hypertension 14. Patients who have unstable angina or a medical history of myocardial infarction within 6 months before enrollment 15. Patients who have diverticulitis or symptomatic peptic ulcer disease 16. Patients who have a history of transplantation therapy, such as hematopoietic stem cell transplantation 17. Patients who have a medical history of treatment with an anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody, anti-CD137 antibody, anti-CTLA-4 antibody, or any other antibody for inhibition or modulation of T cell costimulatory pathway or cancer vaccine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of participants with dose limiting toxicities (DLTs) | from initial dose to 30 post-operative days | To evaluate the safety of combination chemotherapy with nivolumab as neoadjuvant Tx |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete response rate | from baseline to operation, average of 10 weeks after initial dose | To evaluate the efficacy of combination chemotherapy with nivolumab as neoadjuvant Tx |
| Radical resection rate | at operation, average of 10 weeks after initial dose | To evaluate the efficacy of combination chemotherapy with nivolumab as neoadjuvant Tx |
| Treatment completion rate | from baseline to operation, average of 10 weeks after initial dose | To evaluate the efficacy of combination chemotherapy with nivolumab as neoadjuvant Tx |
| Response rate (RR): percentage of participants with with a best response of CR or PR | from baseline to date of disease progression, approximately 24 months | To evaluate the efficacy of combination chemotherapy with nivolumab as neoadjuvant Tx |
| Progression-free survival (PFS) | from baseline to date of disease progression or death, approximately 24 month | To evaluate the efficacy of combination chemotherapy with nivolumab as neoadjuvant Tx |
| Overall survival (OS) | from baseline to date of death, approximately 24 month | To evaluate the efficacy of combination chemotherapy with nivolumab as neoadjuvant Tx |
| Adverse event (AE) expression rate | up to 30 postoperative days | To evaluate the safety of combination chemotherapy with nivolumab as neoadjuvant Tx |
Countries
Japan
Outcome results
None listed