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

NCT04460066 | Unknown Phase 1

• 1 other identifier: ZKAB001-LEES-2020-02
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Esophageal Cancer

Keywords

esophageal cancer; immunotherapy

Outcome Measures

Primary Outcomes (1)

• major pathologic response rate

  The rate of pathologic 1a and 1b after neoadjuvant chemotherapy.

  Two weeks after surgery.

Secondary Outcomes (9)

• R0 resection rate

  Two weeks after surgery.

• pathological complete response rate

  Two weeks after surgery.

• 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.

• 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.

• 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.

Study Arms (2)

PD-L1 group

EXPERIMENTAL

All patients will receive 16 cycles of anti-PD-L1 antibody (5mg/kg, IV, every 3 weeks) , concurrently with 4 cycles of albumin-bound paclitaxel and cisplatin (albumin-bound paclitaxel 125mg/m2 on days 1, 8 and cisplatin 75 mg/m2 on day 1 every 3 weeks).

Drug: anti-PD-L1 antibody; Drug: albumin bound paclitaxel; Drug: cisplatin; Procedure: radical resection of esophageal carcinoma

placebo group

PLACEBO COMPARATOR

All patients will receive 4 cycles of placebo ( IV, every 3 weeks) , concurrently with 4 cycles of albumin-bound paclitaxel and cisplatin (albumin-bound paclitaxel 125mg/m2 on days 1, 8 and cisplatin 75 mg/m2 on day 1 every 3 weeks).

Drug: albumin bound paclitaxel; Drug: cisplatin; Drug: placebo; Procedure: radical resection of esophageal carcinoma

Interventions

anti-PD-L1 antibody DRUG

Patients will receive 16 cycles of anti-PD-L1 antibody 5mg/kg IV on day 1 every 3 weeks.

Also known as: ZKAB001, Socazolimab Injection

PD-L1 group

albumin bound paclitaxel DRUG

Patients will receive 4 cycles of albumin bound paclitaxel 125mg/m2 on days 1, 8 every 3 weeks .

Also known as: ABRAXANE

PD-L1 group; placebo group

cisplatin DRUG

Patients will receive 4 cycles of cisplatin 75mg/m2 on day 1 every 3 weeks.

PD-L1 group; placebo group

placebo DRUG

Patients will receive 4 cycles of placebo IV on day 1 every 3 weeks.

placebo group

radical resection of esophageal carcinoma PROCEDURE

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

PD-L1 group; placebo group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 75 years old of either gender;
• 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;
• ECOG score 0-1;
• Estimated life expectancy \>3 months;
• BMI ≥18.5kg/m2 or PG-SGA score A/B;
• The function of important organs meets the following requirements:
• white blood cell count (WBC) ≥ 3.0×109/L, absolute neutrophil count (ANC) ≥ 1.5×109/L, platelets ≥ 100×109/L, hemoglobin ≥ 90g/L;
• ALT, AST and AKP ≤ 2.5×ULN;
• serum albumin ≥ 30g/L;
• total bilirubin ≤ 1.5×ULN;
• serum creatinine ≤ 1.0×ULN, creatinine clearance rate ≥60 mL/min;
• INR ≤ 1.5, PT≤ 1.5×ULN;
• Cardiac function: ≤I, pulmonary function: FEV1 \>1.2L, FEV1% \>40%, liver function: Child-Pugh 5-6;
• Serum HCG negative in premenopausal women ;
• Ability to understand the study and sign informed consent.

You may not qualify if:

• Cervical esophageal carcinoma;
• Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.);
• Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of anti-PD-L1 antibody and chemotherapeutic drugs;
• Active autoimmune diseases;
• A history of allogeneic stem cell transplantation and organ transplantation;
• A history of interstitial lung disease or non-infectious pneumonia;
• Patients who cannot tolerate chemotherapy or surgery due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia;
• A history of immunodeficiency (including a positive HIV test result), or other acquired or congenital immunodeficiency diseases;
• 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);
• 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;
• A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer;
• Lymph node metastasis in neck, supraclavicular, abdominal cavity, retroperitoneum and pelvic cavity (except paracardial and left gastric lymph nodes).

Sponsors & Collaborators

• Lee's Pharmaceutical Limited: lead

Study Sites (1)

Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, Beijing Municipality, 100000, China

Location

Related Publications (5)

• 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.

  PMID: 9869669 BACKGROUND

• 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.

  PMID: 17028244 BACKGROUND

• 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.

  PMID: 12881388 BACKGROUND

• 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.

  PMID: 25379852 BACKGROUND

• Li Y, Zhou A, Liu S, He M, Chen K, Tian Z, Li Y, Qin J, Wang Z, Chen H, Tian H, Yu Y, Qu W, Xue L, He S, Wang S, Bie F, Bai G, Zhou B, Yang Z, Huang H, Fang Y, Li B, Dai X, Gao S, He J. Comparing a PD-L1 inhibitor plus chemotherapy to chemotherapy alone in neoadjuvant therapy for locally advanced ESCC: a randomized Phase II clinical trial : A randomized clinical trial of neoadjuvant therapy for ESCC. BMC Med. 2023 Mar 8;21(1):86. doi: 10.1186/s12916-023-02804-y.

  PMID: 36882775 DERIVED

Related Links

• GLOBOCAN 2018: oesophagus cancer fact sheet

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

Albumin-Bound Paclitaxel; Cisplatin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• SHUGENG GAO, MD

  Chinese Academy of Medical Sciences and Peking Union Medical College

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2020
• First Posted: July 7, 2020
• Study Start: November 18, 2020
• Primary Completion: December 6, 2021
• Study Completion: July 15, 2023
• Last Updated: May 4, 2022

Record last verified: 2022-04

Locations

CN (1)