Clinical trial NCT04460066: A Study of Anti-PD-L1 Antibody in Neoadjuvant Chemotherapy of Esophageal Squamous Cell Carcinoma.
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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Esophageal Cancer
Keywords: esophageal cancer
immunotherapy
Lead sponsor: Lee's Pharmaceutical Limited
Sponsor class: INDUSTRY
First posted: 2020-07-07
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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).

Primary outcomes:
measure: major pathologic response rate
timeFrame: Two weeks after surgery.
Secondary outcomes:
measure: R0 resection rate
timeFrame: Two weeks after surgery.
measure: pathological complete response rate
timeFrame: Two weeks after surgery.
measure: disease free survival
timeFrame: 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.
measure: disease free survival rate
timeFrame: 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.
measure: event free survival
timeFrame: 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.
measure: event free survival rate
timeFrame: 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.
measure: overall survival rate
timeFrame: 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.
measure: overall survival
timeFrame: 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.
measure: adverse events rate
timeFrame: From the date of randomization to 90 days after the last chemotherapy.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese Academy of Medical Sciences and Peking Union Medical College
state: Beijing
Study officials:
affiliation: Chinese Academy of Medical Sciences and Peking Union Medical College
name: SHUGENG GAO, MD
role: STUDY_DIRECTOR
References:
citation: 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. doi: 10.1056/NEJM199812313392704.
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.
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. doi: 10.1093/annonc/mdg328.
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.