Oesophageal Squamous Cell CarcinomaPhase 2NATION1907IINCT04215471
NeoAdjuvant Therapy With Immunoreagent (SHR-1316) for Resectable Oesophageal Squamous Cell carciNoma
A Phase 2 study testing PD-L1 Antibody SHR-1316 in people with Oesophageal Squamous Cell Carcinoma, run by Shanghai Zhongshan Hospital at 1 site in China.
Trial summary
The investigators will conduct a prospective, single-arm study to evaluate the safety and feasibility of neoadjuvant therapy with anti-PD-L1 antibody (SHR-1316, Hengrui Medicine) in patients with resectable esophageal squamous cell carcinoma (ESCC). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Oesophageal Squamous Cell Carcinoma
- What is being tested?
- PD-L1 Antibody SHR-1316
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 1 Feb 2020to 1 Dec 2022
- Phase
- Phase 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
- The patients should be diagnosed with squamous cell cancer by gastroscopic biopsies and the tissue samples should be collected before the treatment.
- The primary tumor should be located in the thorax; the primary site is decided by the upper margin of the mass (upper thoracic esophagus: from the thoracic inlet to inferior margin of azygos arch, the endoscopic examination shows 20-25cm to the incisor; middle thoracic esophagus: from inferior margin of azygos arch to the inferior pulmonary vein level, the endoscopic examination shows 25-30cm to the incisor; lower thoracic esophagus: from the inferior pulmonary vein level to the stomach, the endoscopic examination shows 30-40cm to the incisor).
- The patients should be evaluated to be able to have surgical resection before the surgery according to the examinations (use enhanced thoracic and abdominal CT, cervical lymph node ultrasound to evaluate whether the tumor has obvious invasion, whether there are enlarged mediastinal lymph nodes; use examinations including positron emission computed tomography (PET-CT), endoscopic ultrasonography (EUS) to make further clinical staging if considering the primary tumor as T4b, multiple mediastinal lymph nodes metastasis or distant metastasis).
- The patients should be at the range of 18-75 years old, Eastern Cooperative Oncology Group (ECOG) 0-1, the estimated survival time should be over 12 months.
- The recipients should have no functional disorders in main organs. Blood routines, functions of lung, liver, kidney and heart should be basically normal, the label test index should accord with the demands as follows: Blood: white blood cell count (WBC)>4.0*10^9/L, absolute neutrophil count (ANC)≥2.0*10^9/L, platelet count (PLT)>100*10^9/L, hemoglobin (HBG)>90g/L; Pulmonary function: Forced Expiratory Volume in the first second (FEV1)≥1.2 L, FEV1%≥50%, carbon monoxide diffusing capacity (DLCO)≥50%; Liver function: Serum bilirubin should be lower than 1.5 times of the maximum normal value; Alanine aminotransferase (ALT) and Aspartate transaminase (AST) should be lower than 1.5 times of the maximum normal value; Renal function: serum creatinine (SCr)≤120μmol/L creatinine clearance rate （CCr）≥60ml/min;
- The patients should be able to understand our research and sign the informed consent.
Who cannot join
- The stage of tumor is T4b (AJCC/International Union Against Cancer (UICC) 8th Edition) which can not be resected according to imaging examinations like thoracic and abdominal enhanced CT, cervical lymph nodes ultrasound, whole body PET-CT scan (optional) or endobronchial ultrasonography (EBUS) (optional); several enlarged lymph nodes existed (≥3 estimated lymph nodes metastasis); multiple station enlarged lymph nodes existed (≥2 estimated stations of lymph nodes metastasis); distant metastasis existed.
- The patients have accepted or are on the process of other chemotherapy, radiotherapy or targeted therapy.
- Endoscopic examination shows non-squamous carcinoma.
- The patients have history of other tumors (not include history of carcinoma in situ of the cervix, cured localized skin basal cell carcinoma).
- Other exclusion criteria:
- The patients have history of autoimmune diseases.
Show all 20Show fewer
- The patients have recently taken steroids or immune immunosuppressive agents or are taking them.
- The patients have history of immunotherapy.
- The patients have history of severe hypersensitivity to antibody drugs.
- The patients have history of chronic or recurrent autoimmune diseases.
- The patients have interstitial lung disease, pulmonary fibrosis, diverticulitis or systematic ulcerative gastritis.
- The patients have proved history of congestive heart failure, angina without good control with medicine; ECG-proved penetrating myocardial infarction; hypertension with bad control; valvulopathy with clinical significance; arrhythmia with high risk and out of control.
- The patients have severe systematic intercurrent disease, such as active infection or poorly controlled diabetes; coagulation disorders; hemorrhagic tendency or under treatment of thrombolysis or anticoagulant therapy.
- Female who is positive for serum pregnancy test or during lactation period, or people at child bearing stage who are reluctant to use contraception measures during the research.
- The patients have active infection of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV) or be HIV serum positive; or HBV, HCV RNA positive.
- The patients are allergic for any of the drugs in the research.
- The patients have history of organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation.
- The patients have history of peripheral nerve system disorders, obvious mental disorders or central nerve system disorders.
- The patients are using other anti-tumor drugs.
- The patients attend other clinical trials.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
180 Fenglin Road
Shanghai, 200032
Jun Yin, MD, +86-21-64401991 ext. 2017, yin.jun2@zs-hospital.sh.cn
About this study
Official title: The Safety and Feasibility of NeoAdjuvant Therapy With Immunoreagent (PD-L1 Antibody SHR-1316) for Resectable Oesophageal Squamous Cell carciNoma (NATION1907II)
The investigators will conduct a prospective, single-arm study to evaluate the safety and feasibility of neoadjuvant therapy with anti-PD-L1 antibody (SHR-1316, Hengrui Medicine) in patients with resectable esophageal squamous cell carcinoma (ESCC).
Read the detailed description
Host immunity is critical to the development and progression of tumor. PD-1 is the co-inhibitory receptor in many immunity cells while PD-L1, the ligands for PD-1, is expressed in tumor cell and is associated with prognosis. Previous studies have shown that anti-PD-1/PD-L1 antibody had durable responses in patients with advanced malignant tumors such as melanoma, renal cell cancer, lung cancer and esophagus cancer. SHR-1316 (Hengrui Medicine, China), anti-PD-L1 antibody, could induce the elevated secretion of interferon (IFN)-α and showed significant tumor-suppression effect in vivo. The phase III clinical trial on the SHR-1316 versus placebo combines with carboplatin and etoposide in the patients with small cell lung cancer is currently being studied (SHR-1316-III-301).
Esophagus cancer usually has a poor prognosis and esophagus squamous cell carcinoma (ESCC) is the main histological type in China. Combination with operation and neoadjuvant therapy including radiotherapy or/and chemotherapy is considered the standard therapy for local advanced esophagus cancer. However, no studies focused on the neoadjuvant immunotherapy in resectable esophagus have been reported.
Therefore, the investigators will conduct a prospective, single-arm study to evaluate the safety and feasibility of neoadjuvant therapy with anti-PD-L1 antibody (SHR-1316, Hengrui Medicine) in patients with resectable ESCC. The primary objectives included the tumor regression grade, adverse event, safety of operation, complications and 30-day mortality. Our study will also explore the relation of tumor immune milieu, circulating immune cells, soluble factors, circulating tumor cell in the patients. Data from our study will provide the basis for further prospective clinical trials (Phase III). Finally, the investigators aim to discover the biomarkers of response and toxicity to allow patients with ESCC derive more benefit from immunotherapy and minimize the risk of toxicity.
- Conditions
- Oesophageal Squamous Cell Carcinoma
- Being tested
- PD-L1 Antibody SHR-1316
- Medical subject headings
- Esophageal Squamous Cell Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD-L1 Antibody SHR-1316Drug
Also called PD-L1 antibody
Neoadjuvant therapy with immunoreagent (PD-L1 antibody SHR-1316) for resectable oesophageal squamous cell carcinoma
| Study group | Role | What they receive |
|---|---|---|
| NeoAdjuvant Therapy With PD-L1 Antibody SHR-1316 group | Experimental | Patients will receive the neoadjuvant therapy with SHR-1316 followed by the operation. Receives: Drug: PD-L1 Antibody SHR-1316 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response
The primary endpoint is objective response (according to the Response Evaluation Criteria In Solid Tumors, version 1.1).
Measured: Through the study completion, an average of 12 weeks
Secondary outcomes (2)
Adverse events and treatment-related adverse events
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: Through the study completion, an average of 12 weeks
Correlation between genetic profile and tumor response
Genetic profile (assessed by whole exome sequencing, T-cell receptor sequencing, RNA sequencing) will be correlated with tumor objective response
Measured: Through the study completion, an average of 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2020
- Study start1 Feb 2020
- Primary completion1 Jul 2022 (estimated)
- Study completion1 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Oesophageal Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Shanghai Zhongshan HospitalThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Zhongshan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lijie Tan, MD, PhD, Principal investigator, Shanghai Zhongshan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04215471
- Sponsor's protocol ID
- B2019-205R
- Acronym
- NATION1907II
- Status last verified
- Jun 2022
- First submitted
- 27 Dec 2019
- Last updated
- 14 Jun 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data (IPD) will be shared
Publications
Yin J, Yuan J, Li Y, Fang Y, Wang R, Jiao H, Tang H, Zhang S, Lin S, Su F, Gu J, Jiang T, Lin D, Huang Z, Du C, Wu K, Tan L, Zhou Q. Neoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial. Nat Med. 2023 Aug;29(8):2068-2078. doi: 10.1038/s41591-023-02469-3. Epub 2023 Jul 24.
PubMed 37488287
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety and Feasibility of NeoAdjuvant Therapy With Immunoreagent (PD-L1 Antibody SHR-1316) for Resectable Oesophageal Squamous Cell carciNoma (NATION1907II)
- ClinicalTrials.gov ID
- NCT04215471
- Acronym / sponsor ID
- NATION1907II / B2019-205R
- Conditions
- Oesophageal Squamous Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Shanghai Zhongshan HospitalUniversity, hospital or other
- Study start
- 1 Feb 2020 (actual)
- Primary completion
- 1 Jul 2022 (estimated)
- Study completion
- 1 Dec 2022 (estimated)
- First posted
- 2 Jan 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.
The investigators will conduct a prospective, single-arm study to evaluate the safety and feasibility of neoadjuvant therapy with anti-PD-L1 antibody (SHR-1316, Hengrui Medicine) in patients with resectable esophageal squamous cell carcinoma (ESCC).
Detailed description
Host immunity is critical to the development and progression of tumor. PD-1 is the co-inhibitory receptor in many immunity cells while PD-L1, the ligands for PD-1, is expressed in tumor cell and is associated with prognosis. Previous studies have shown that anti-PD-1/PD-L1 antibody had durable responses in patients with advanced malignant tumors such as melanoma, renal cell cancer, lung cancer and esophagus cancer. SHR-1316 (Hengrui Medicine, China), anti-PD-L1 antibody, could induce the elevated secretion of interferon (IFN)-α and showed significant tumor-suppression effect in vivo. The phase III clinical trial on the SHR-1316 versus placebo combines with carboplatin and etoposide in the patients with small cell lung cancer is currently being studied (SHR-1316-III-301).
Esophagus cancer usually has a poor prognosis and esophagus squamous cell carcinoma (ESCC) is the main histological type in China. Combination with operation and neoadjuvant therapy including radiotherapy or/and chemotherapy is considered the standard therapy for local advanced esophagus cancer. However, no studies focused on the neoadjuvant immunotherapy in resectable esophagus have been reported.
Therefore, the investigators will conduct a prospective, single-arm study to evaluate the safety and feasibility of neoadjuvant therapy with anti-PD-L1 antibody (SHR-1316, Hengrui Medicine) in patients with resectable ESCC. The primary objectives included the tumor regression grade, adverse event, safety of operation, complications and 30-day mortality. Our study will also explore the relation of tumor immune milieu, circulating immune cells, soluble factors, circulating tumor cell in the patients. Data from our study will provide the basis for further prospective clinical trials (Phase III). Finally, the investigators aim to discover the biomarkers of response and toxicity to allow patients with ESCC derive more benefit from immunotherapy and minimize the risk of toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NeoAdjuvant Therapy With PD-L1 Antibody SHR-1316 group | Experimental | Drug: PD-L1 Antibody SHR-1316Patients will receive the neoadjuvant therapy with SHR-1316 followed by the operation. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- The patients should be diagnosed with squamous cell cancer by gastroscopic biopsies and the tissue samples should be collected before the treatment.
- The primary tumor should be located in the thorax; the primary site is decided by the upper margin of the mass (upper thoracic esophagus: from the thoracic inlet to inferior margin of azygos arch, the endoscopic examination shows 20-25cm to the incisor; middle thoracic esophagus: from inferior margin of azygos arch to the inferior pulmonary vein level, the endoscopic examination shows 25-30cm to the incisor; lower thoracic esophagus: from the inferior pulmonary vein level to the stomach, the endoscopic examination shows 30-40cm to the incisor).
- The patients should be evaluated to be able to have surgical resection before the surgery according to the examinations (use enhanced thoracic and abdominal CT, cervical lymph node ultrasound to evaluate whether the tumor has obvious invasion, whether there are enlarged mediastinal lymph nodes; use examinations including positron emission computed tomography (PET-CT), endoscopic ultrasonography (EUS) to make further clinical staging if considering the primary tumor as T4b, multiple mediastinal lymph nodes metastasis or distant metastasis).
- The patients should be at the range of 18-75 years old, Eastern Cooperative Oncology Group (ECOG) 0-1, the estimated survival time should be over 12 months.
- The recipients should have no functional disorders in main organs. Blood routines, functions of lung, liver, kidney and heart should be basically normal, the label test index should accord with the demands as follows: Blood: white blood cell count (WBC)>4.0*10^9/L, absolute neutrophil count (ANC)≥2.0*10^9/L, platelet count (PLT)>100*10^9/L, hemoglobin (HBG)>90g/L; Pulmonary function: Forced Expiratory Volume in the first second (FEV1)≥1.2 L, FEV1%≥50%, carbon monoxide diffusing capacity (DLCO)≥50%; Liver function: Serum bilirubin should be lower than 1.5 times of the maximum normal value; Alanine aminotransferase (ALT) and Aspartate transaminase (AST) should be lower than 1.5 times of the maximum normal value; Renal function: serum creatinine (SCr)≤120μmol/L creatinine clearance rate （CCr）≥60ml/min;
Key exclusion criteria (20 listed)
- The stage of tumor is T4b (AJCC/International Union Against Cancer (UICC) 8th Edition) which can not be resected according to imaging examinations like thoracic and abdominal enhanced CT, cervical lymph nodes ultrasound, whole body PET-CT scan (optional) or endobronchial ultrasonography (EBUS) (optional); several enlarged lymph nodes existed (≥3 estimated lymph nodes metastasis); multiple station enlarged lymph nodes existed (≥2 estimated stations of lymph nodes metastasis); distant metastasis existed.
- The patients have accepted or are on the process of other chemotherapy, radiotherapy or targeted therapy.
- Endoscopic examination shows non-squamous carcinoma.
- The patients have history of other tumors (not include history of carcinoma in situ of the cervix, cured localized skin basal cell carcinoma).
- The patients have history of autoimmune diseases.
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 |
|---|---|---|
| PD-L1 Antibody SHR-1316Also: PD-L1 antibodyNeoadjuvant therapy with immunoreagent (PD-L1 antibody SHR-1316) for resectable oesophageal squamous cell carcinoma | Drug | NeoAdjuvant Therapy With PD-L1 Antibody SHR-1316 group |
Primary outcome
Objective Response
Time frame: Through the study completion, an average of 12 weeks
The primary endpoint is objective response (according to the Response Evaluation Criteria In Solid Tumors, version 1.1).
2 secondary outcomes
Adverse events and treatment-related adverse events
Time frame: Through the study completion, an average of 12 weeks
Correlation between genetic profile and tumor response
Time frame: Through the study completion, an average of 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2022.
- Derived from this study: PubMed 37488287Yin J, Yuan J, Li Y, Fang Y, Wang R, Jiao H, Tang H, Zhang S, Lin S, Su F, Gu J, Jiang T, Lin D, Huang Z, Du C, Wu K, Tan L, Zhou Q. Neoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial. Nat Med. 2023 Aug;29(8):2068-2078. doi: 10.1038/s41591-023-02469-3. Epub 2023 Jul 24.
- Individual participant dataSharing planned: Yes. Individual participant data (IPD) will be shared
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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.
Lijie Tan, MD, PhD principal investigator
Shanghai Zhongshan Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PD-L1 Antibody SHR-1316 in people with Oesophageal Squamous Cell Carcinoma, run by Shanghai Zhongshan Hospital 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 6 inclusion and 20 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 14 Jun 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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?
Contact Lijie Tan, MD, PhD (8613681972151, tan.lijie@zs-hospital.sh.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response (time frame: Through the study completion, an average of 12 weeks). 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 NCT04215471, which also lists 1 linked publication.
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 14 Jun 2022.