Esophageal CancerPhase 1/2NCT04460066
A Study of Anti-PD-L1 Antibody in Neoadjuvant Chemotherapy of Esophageal Squamous Cell Carcinoma.
A Phase 1/2 study testing anti-PD-L1 antibody, albumin bound paclitaxel and cisplatin in people with Esophageal Cancer, run by Lee's Pharmaceutical Limited at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Esophageal Cancer
- What is being tested?
- anti-PD-L1 antibody, albumin bound paclitaxel and cisplatin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteChina
- Study dates
- 18 Nov 2020to 15 Jul 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 15Show fewer
- 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.
Who cannot join
- 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;
Show all 12Show fewer
- 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).
Trial locations and contacts
1 site in 1 country.
China1 site
Chinese Academy of Medical Sciences and Peking Union Medical College
Beijing, Beijing Municipality, 100000
About this study
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.
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
- Being tested
- anti-PD-L1 antibody, albumin bound paclitaxel, cisplatin, placebo, radical resection of esophageal carcinoma
- Keywords
- esophageal cancer, immunotherapy
- Medical subject headings
- Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-PD-L1 antibodyDrug
Also called ZKAB001, Socazolimab Injection
Patients will receive 16 cycles of anti-PD-L1 antibody 5mg/kg IV on day 1 every 3 weeks.
albumin bound paclitaxelDrug
Also called ABRAXANE
Patients will receive 4 cycles of albumin bound paclitaxel 125mg/m2 on days 1, 8 every 3 weeks .
cisplatinDrug
Patients will receive 4 cycles of cisplatin 75mg/m2 on day 1 every 3 weeks.
placeboDrug
Patients will receive 4 cycles of placebo IV on day 1 every 3 weeks.
radical resection of esophageal carcinomaProcedure or surgery
Patients will receive radical resection of esophageal carcinoma after 4 cycles of chemotherapy.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Drug: albumin bound paclitaxel; Drug: cisplatin; Drug: placebo; Procedure: radical resection of esophageal carcinoma |
What is being measured
The primary outcome is the main question the study is designed to answer.
major pathologic response rate
The rate of pathologic 1a and 1b after neoadjuvant chemotherapy.
Measured: Two weeks after surgery.
Secondary outcomes (9)
R0 resection rate
The R0 resection rate of esophagectomy.
Measured: Two weeks after surgery.
pathological complete response rate
The rate of pathologic 1a after neoadjuvant chemotherapy.
Measured: Two weeks after surgery.
disease free survival
The 2-year disease free survival of the whole group.
Measured: 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
The 2-year disease free survival rate of the whole group.
Measured: 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
The 2-year event free survival of the whole group.
Measured: 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.
event free survival rate
The 2-year event free survival rate of the whole group.
Measured: 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.
overall survival rate
The 2-year overall survival rate of the whole group.
Measured: 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.
overall survival
The 2-year overall survival of the whole group.
Measured: 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.
adverse events rate
The incidence rate of treatment-related adverse events of the whole group assessed by CTCAE v5.0.
Measured: From the date of randomization to 90 days after the last chemotherapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2020
- Study start18 Nov 2020
- Primary completion6 Dec 2021
- Study completion15 Jul 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Esophageal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lee's Pharmaceutical Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- SHUGENG GAO, MD, Study director, Chinese Academy of Medical Sciences and Peking Union Medical College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04460066
- Sponsor's protocol ID
- ZKAB001-LEES-2020-02
- Status last verified
- Apr 2022
- First submitted
- 1 Jul 2020
- Last updated
- 4 May 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 9869669Lin 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.
PubMed 17028244Polee 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.
PubMed 12881388Shapiro 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.
PubMed 25379852Li 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.
PubMed 36882775
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT04460066
- Acronym / sponsor ID
- ZKAB001-LEES-2020-02
- Conditions
- Esophageal Cancer
- Keywords
- esophageal cancer, immunotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Lee's Pharmaceutical LimitedIndustry (pharma, biotech, devices)
- Study start
- 18 Nov 2020 (actual)
- Primary completion
- 6 Dec 2021 (actual)
- Study completion
- 15 Jul 2023 (estimated)
- First posted
- 7 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PD-L1 group | Experimental | Drug: anti-PD-L1 antibody, Drug: albumin bound paclitaxel, Drug: cisplatin, Procedure: radical resection of esophageal carcinomaAll 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). |
| placebo group | Placebo comparator | Drug: albumin bound paclitaxel, Drug: cisplatin, Drug: placebo, Procedure: radical resection of esophageal carcinomaAll 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). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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;
Key exclusion criteria (12 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| anti-PD-L1 antibodyAlso: ZKAB001, Socazolimab InjectionPatients will receive 16 cycles of anti-PD-L1 antibody 5mg/kg IV on day 1 every 3 weeks. | Drug | PD-L1 group |
| albumin bound paclitaxelAlso: ABRAXANEPatients will receive 4 cycles of albumin bound paclitaxel 125mg/m2 on days 1, 8 every 3 weeks . | Drug | PD-L1 group, placebo group |
| cisplatinPatients will receive 4 cycles of cisplatin 75mg/m2 on day 1 every 3 weeks. | Drug | PD-L1 group, placebo group |
| placeboPatients will receive 4 cycles of placebo IV on day 1 every 3 weeks. | Drug | placebo group |
| radical resection of esophageal carcinomaPatients will receive radical resection of esophageal carcinoma after 4 cycles of chemotherapy. | Procedure or surgery | PD-L1 group, placebo group |
Primary outcome
major pathologic response rate
Time frame: Two weeks after surgery.
The rate of pathologic 1a and 1b after neoadjuvant chemotherapy.
9 secondary outcomes
R0 resection rate
Time frame: Two weeks after surgery.
pathological complete response rate
Time frame: Two weeks after surgery.
disease free survival
Time frame: 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
Time frame: 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
Time frame: 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.
event free survival rate
Time frame: 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.
overall survival rate
Time frame: 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.
overall survival
Time frame: 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.
adverse events rate
Time frame: From the date of randomization to 90 days after the last chemotherapy.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2022.
- Background: PubMed 9869669Kelsen 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.
- Background: PubMed 17028244Lin 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.
- Background: PubMed 12881388Polee 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.
- Background: PubMed 25379852Shapiro 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.
- Derived from this study: PubMed 36882775Li 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.
- GLOBOCAN 2018: oesophagus cancer fact sheetLink provided by the sponsor.
Related trials for Esophageal Cancer
RecruitingPhase 2/3
Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types
Oesophageal Cancer, Gastric Cancer
RecruitingObservational study
Multicenter Prospective Cohort on Esophageal Endoscopic Submucosal Dissection
Superficial Esophageal Cancer, Oesophageal Adenocarcinoma
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
SHUGENG GAO, MD study director
Chinese Academy of Medical Sciences and Peking Union Medical College
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing anti-PD-L1 antibody, albumin bound paclitaxel and cisplatin in people with Esophageal Cancer, run by Lee's Pharmaceutical Limited at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
major pathologic response rate (time frame: Two weeks after surgery.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04460066, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2022.