Esophageal Cancer
Conditions
Keywords
esophageal cancer, immunotherapy
Brief summary
This is a randomized, double-blind, placebo-controlled Ib/Ⅱ clinical study to evaluate the safety and effect of anti-PD-L1 antibody (ZKAB001) in neoadjuvant chemotherapy of esophageal squamous carcinoma in combination with Alb-paclitaxel and cisplatin. The immunotherapy will be given before and after the operation every three weeks.
Interventions
Patients will receive 16 cycles of anti-PD-L1 antibody 5mg/kg IV on day 1 every 3 weeks.
Patients will receive 4 cycles of albumin bound paclitaxel 125mg/m2 on days 1, 8 every 3 weeks .
DRUGcisplatin
Patients will receive 4 cycles of cisplatin 75mg/m2 on day 1 every 3 weeks.
DRUGplacebo
Patients will receive 4 cycles of placebo IV on day 1 every 3 weeks.
PROCEDUREradical resection of esophageal carcinoma
Patients will receive radical resection of esophageal carcinoma after 4 cycles of chemotherapy.
Sponsors
Lee's Pharmaceutical Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key inclusion Criteria: 1. Aged 18 to 75 years old of either gender; 2. A histopathological diagnosis of esophageal squamous cell carcinoma with a clinical stage of T2N+M0 or T3-4aN+/-M0 according to the 8th edition of the UICC staging system; 3. ECOG score 0-1; 4. Estimated life expectancy \>3 months; 5. BMI ≥18.5kg/m2 or PG-SGA score A/B; 6. The function of important organs meets the following requirements: 1. white blood cell count (WBC) ≥ 3.0×109/L, absolute neutrophil count (ANC) ≥ 1.5×109/L, platelets ≥ 100×109/L, hemoglobin ≥ 90g/L; 2. ALT, AST and AKP ≤ 2.5×ULN; 3. serum albumin ≥ 30g/L; 4. total bilirubin ≤ 1.5×ULN; 5. serum creatinine ≤ 1.0×ULN, creatinine clearance rate ≥60 mL/min; 6. INR ≤ 1.5, PT≤ 1.5×ULN; 7. Cardiac function: ≤I, pulmonary function: FEV1 \>1.2L, FEV1% \>40%, liver function: Child-Pugh 5-6; 8. Serum HCG negative in premenopausal women ; 9. Ability to understand the study and sign informed consent. Key
Exclusion criteria
1. Cervical esophageal carcinoma; 2. Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.); 3. Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of anti-PD-L1 antibody and chemotherapeutic drugs; 4. Active autoimmune diseases; 5. A history of allogeneic stem cell transplantation and organ transplantation; 6. A history of interstitial lung disease or non-infectious pneumonia; 7. Patients who cannot tolerate chemotherapy or surgery due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia; 8. A history of immunodeficiency (including a positive HIV test result), or other acquired or congenital immunodeficiency diseases; 9. Presence of active hepatitis B (HBV DNA ≥ 200 IU/mL or 103 copies/mL), hepatitis C (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit of the assay); 10. 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; 11. A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer; 12. Lymph node metastasis in neck, supraclavicular, abdominal cavity, retroperitoneum and pelvic cavity (except paracardial and left gastric lymph nodes).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| major pathologic response rate | Two weeks after surgery. | The rate of pathologic 1a and 1b after neoadjuvant chemotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| pathological complete response rate | Two weeks after surgery. | The rate of pathologic 1a after neoadjuvant chemotherapy. |
| disease free survival | From the date of surgery until the date of death due to disease progression 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. |
| disease free survival rate | From the date of surgery until the date of death due to disease progression or the date of first documented disease progression whichever came first, assessed up to 24 months. | The 2-year disease free survival rate of the whole group. |
| event free survival | From the date of randomization 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 event free survival of the whole group. |
| R0 resection rate | Two weeks after surgery. | The R0 resection rate of esophagectomy. |
| overall survival rate | From the 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 rate of the whole group. |
| overall survival | From the 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. |
| adverse events rate | From the date of randomization to 90 days after the last chemotherapy. | The incidence rate of treatment-related adverse events of the whole group assessed by CTCAE v5.0. |
| event free survival rate | From the date of randomization 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 event free survival rate of the whole group. |
Countries
China
Outcome results
None listed