A Study of Anti-PD-L1 Antibody in Neoadjuvant Chemotherapy of Esophageal Squamous Cell Carcinoma.

Esophageal Cancer Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled Phase Ib/II Clinical Study of Anti-pd-l1 Monoclonal Antibody Injection (ZKAB001) Combined Albumin Binding Paclitaxel, Cisplatin in Neoadjuvant Treatment of Esophageal Squamous Cell Carcinoma.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04460066
• Other study ID #: ZKAB001-LEES-2020-02
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: November 18, 2020
• Est. completion date: July 15, 2023

Study information

• Verified date: April 2022
• Source: Lee's Pharmaceutical Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 70
• Est. completion date: July 15, 2023
• Est. primary completion date: December 6, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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).

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Esophageal Cancer
• Esophageal Neoplasms
• Esophageal Squamous Cell Carcinoma

Intervention

Drug:
• anti-PD-L1 antibody
Patients will receive 16 cycles of anti-PD-L1 antibody 5mg/kg IV on day 1 every 3 weeks.
• albumin bound paclitaxel
Patients will receive 4 cycles of albumin bound paclitaxel 125mg/m2 on days 1, 8 every 3 weeks .
• cisplatin
Patients will receive 4 cycles of cisplatin 75mg/m2 on day 1 every 3 weeks.
• placebo
Patients will receive 4 cycles of placebo IV on day 1 every 3 weeks.

Procedure:
• radical resection of esophageal carcinoma
Patients will receive radical resection of esophageal carcinoma after 4 cycles of chemotherapy.

Locations

Country	Name	City	State
China	Chinese Academy of Medical Sciences and Peking Union Medical College	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Lee's Pharmaceutical Limited

Country where clinical trial is conducted

China, 

References & Publications (4)

Kelsen DP, Ginsberg R, Pajak TF, Sheahan DG, Gunderson L, Mortimer J, Estes N, Haller DG, Ajani J, Kocha W, Minsky BD, Roth JA. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med. 1998 Dec 31;339(27):1979-84. — View Citation

Lin CC, Hsu CH, Cheng JC, Wang HP, Lee JM, Yeh KH, Yang CH, Lin JT, Cheng AL, Lee YC. Concurrent chemoradiotherapy with twice weekly paclitaxel and cisplatin followed by esophagectomy for locally advanced esophageal cancer. Ann Oncol. 2007 Jan;18(1):93-98. doi: 10.1093/annonc/mdl339. Epub 2006 Oct 6. — View Citation

Polee MB, Tilanus HW, Eskens FA, Hoekstra R, Van der Burg ME, Siersema PD, Stoter G, Van der Gaast A. Phase II study of neo-adjuvant chemotherapy with paclitaxel and cisplatin given every 2 weeks for patients with a resectable squamous cell carcinoma of the esophagus. Ann Oncol. 2003 Aug;14(8):1253-7. — View Citation

Shapiro J, van Hagen P, Lingsma HF, Wijnhoven BP, Biermann K, ten Kate FJ, Steyerberg EW, van der Gaast A, van Lanschot JJ; CROSS Study Group. Prolonged time to surgery after neoadjuvant chemoradiotherapy increases histopathological response without affecting survival in patients with esophageal or junctional cancer. Ann Surg. 2014 Nov;260(5):807-13; discussion 813-4. doi: 10.1097/SLA.0000000000000966. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	major pathologic response rate	The rate of pathologic 1a and 1b after neoadjuvant chemotherapy.	Two weeks after surgery.
Secondary	R0 resection rate	The R0 resection rate of esophagectomy.	Two weeks after surgery.
Secondary	pathological complete response rate	The rate of pathologic 1a after neoadjuvant chemotherapy.	Two weeks after surgery.
Secondary	disease free survival	The 2-year disease free survival of the whole group.	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.
Secondary	disease free survival rate	The 2-year disease free survival rate of the whole group.	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.
Secondary	event free survival	The 2-year event free survival of the whole group.	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.
Secondary	event free survival rate	The 2-year event free survival rate of the whole group.	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.
Secondary	overall survival rate	The 2-year overall survival rate of the whole group.	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.
Secondary	overall survival	The 2-year overall survival of the whole group.	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.
Secondary	adverse events rate	The incidence rate of treatment-related adverse events of the whole group assessed by CTCAE v5.0.	From the date of randomization to 90 days after the last chemotherapy.

External Links

•   GLOBOCAN 2018: oesophagus cancer fact sheet