Esophagus CancerPhase 2T+TPNCT04177875
Neoadjuvant Chemoradiotherapy Combined With PD-1 Antibody in Locally Advanced Esophageal Cancer
A Phase 2 study testing Teripalimab in people with Esophagus Cancer, run by Tongji Hospital at 1 site in China.
Trial summary
This study will evaluate the safety and feasibility of preoperative immune checkpoint therapy with concurrent Chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Esophagus Cancer
- What is being tested?
- Teripalimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteChina
- Study dates
- 1 May 2019to 30 Apr 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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18-70, male or female
- Locally advanced esophageal cancer diagnosed by pathology, Clinical tumor stage should be T2-3N0-1M0
- No previous chemoradiotherapy
- Have a performance status of 0 or 1 on the ECOG Performance Scale
- Demonstrate adequate organ function as defined below (excluding the use of any blood components and cytokines during the screening period)
- Absolute neutrophil count (ANC) ≥1.5*109 /L; Platelet ≥90*109/L; Hemoglobin ≥ 9 g/dL; Serum albumin≥3g/dL
Show all 9Show fewer
- Bilirubin≤1.5 x ULN; ALT and AST≤2.5 ULN; Serum creatinine ≤1.5 x ULN or creatinine clearance ≥40mL/min
- Female subject must have taken reliable contraceptive measures of childbearing potential should have a negative urine or serum pregnancy within 7 days prior to receiving the first dose of study medication. and be willing to use an appropriate method of contraception during the trial and 8 weeks after the last administration of the test drug. Male subject should agree to use appropriate contraceptive methods or to have been surgically sterilized during the trial and 8 weeks after the last administration of the test drug.
- Subjects voluntarily participated in this study and signed the informed consent, with good compliance and follow-up.
Who cannot join
- Any active autoimmune disease or history of autoimmune disease (as follows, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitritis, vasculitis, nephritis, hyperthyroidism, thyroid dysfunction);Subjects with vitiligo or who have had complete remission from childhood asthma without any intervention after adulthood may be included; Asthma requiring medical intervention with bronchodilators was not included. Those who have used other drugs in clinical trials to study drugs within 4 weeks before their first use;
- Severe allergic reaction to monoclonal antibody
- The number of neutrophils in peripheral blood was lower than 1500/mm3;
- There are clinical symptoms or diseases of the heart that are not well controlled, such as: A. heart failure above grade 2 by the Criteria of NYHA; B. unstable angina pectoris; C. myocardial infarction occurred within 1 year; D. Clinically meaningful supraventricular or ventricular arrhythmias require treatment or intervention;
- Has a previous radiotherapy, chemotherapy, hormone therapy, surgery or molecular targeted therapy;
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). or Has known active Hepatitis B (e.g. HBV DNA≥ 2000IU/ml or copy number ≥104/ml;) or Hepatitis C (e.g. HCV antibody positive).
- According to the judgment of the researchers, the subjects have other factors that may cause the forced termination of the study, such as other serious diseases (including mental diseases) requiring combined treatment, severe laboratory examination abnormalities, accompanied by family or social factors, which may affect the safety of the subjects, or the collection of data and samples.
- The researchers determined patients with high risk of esophageal perforation or no potential surgical feasibility through endoscopic ultrasonography or imaging examination.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
Wuhan, Hubei, 430030
li Zhang, PhD
About this study
Official title: A Phase II, Prospective, Open-label Clinical Trial of Pre-Operative PD-1 Antibody (Toripalimab) + Chemoradiotherapy in Patients With Locally Advanced Esophageal Cancer
This study will evaluate the safety and feasibility of preoperative immune checkpoint therapy with concurrent Chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. And this study will provide valuable information for further clinical trials of preoperative Teripalimab and other immune checkpoint therapy in esophageal cancer treatment.
Read the detailed description
Esophageal cancer ranks the eighth most common cancer in Worldwide. And the third among men and the fifth among women in China, among which esophageal squamous cell carcinoma accounts for about 90%.
Neoadjuvant therapy for esophageal cancer is increasingly supported by evidence. However, the results of neoadjuvant therapy are not completely consistent. Most studies of neoadjuvant treatment data for esophageal cancer were obtained from western populations, where esophageal adenocarcinoma and esophagogastric junction adenocarcinoma were more common and the sample size was relatively small. According to the meta-analysis of the reported results of randomized controlled trials, concurrent chemoradiotherapy has a higher pathological complete response rate than chemotherapy alone as neoadjuvant therapy. However, the 3-year survival rate of neoadjuvant chemoradiotherapy only showed an advantage in patients with squamous cell carcinoma (56.8%vs42.8%), but no significant difference in patients with adenocarcinoma (46.3%vs41.0%). Pathological complete remission rate of esophageal cancer after neoadjuvant chemotherapy is relatively low.
It can be seen that positive expression of programmed death ligand-1 is more common in Esophageal squamous cell carcinoma, and programmed death ligand-1 tends to be overexpressed compared with adjacent normal epithelial cells. The later the T-stage of the tumor, the higher the positive expression rate. In addition, programmed death ligand-1 expression is significantly correlated with lymphatic metastasis. Therefore, programmed death ligand-1 expression can promote tumor progression. The recurrence rate of patients with programmed death ligand-1 expression is higher after treatment, and the postoperative complete pathological remission rate is lower in programmed death ligand-1 positive patients. In addition, positive programmed death ligand-1 expression also reduces the sensitivity of radiotherapy, which may be contributing factors to poor prognosis of patients with positive pd-l1 expression. It is worth mentioning that clinical treatment will affect the expression level of programmed death ligand-1 in esophageal cancer tissues. Neoadjuvant concurrent chemoradiotherapy can up-regulate the expression of programmed death ligand-1 in ESCC significantly, while neoadjuvant chemotherapy can down-regulate the expression of pd-L1. However, radiotherapy can up-regulate the expression level of programmed death ligand-1 in esophageal cancer cells, which is positively correlated with radiation dose, and the combination of anti-pd-L1 therapy and radiotherapy can lead to increased tumor cell lysis, which also indicates the importance of comprehensive treatment of tumor.
There are relatively few studies on the treatment of esophageal cancer with pd-1 / pd-L1 inhibitors. Keynote-059 enrolled 259 patients with advanced gastric or gastroesophageal junction cancer in the phase II clinical trial of Pembrolizumab, with an objective response rate of 11.6%, complete response rate of 2.3%, and median response duration of 8.4 months. Persistent objective response rates were observed in both programmed death ligand-1 positive and negative patients, and adverse reactions were tolerable.
The efficacy and safety of anti-pd-1 / pd-L1 therapy in the treatment of esophageal cancer still need a lot of clinical studies to further confirm. This study will evaluate the safety and feasibility of preoperative immune checkpoint therapy using pembrolizumab with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. And this study will provide valuable information for further clinical trials of preoperative Teripalimab and other immune checkpoint therapy in esophageal cancer.
- Conditions
- Esophagus Cancer
- Being tested
- Teripalimab
- Keywords
- neoadjuvant therapy；pd-1 antibody combined with Chemoradiotherapy
- Medical subject headings
- Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TeripalimabDrug
Also called Docetaxel /Albumin-bound Paclitaxel, Cisplatin
Teripalimab Injection 240mg/6ml fixed dose (3mg/kg for patients weighing less than 40kg) ,injection on day 1, each infusion for 30min (no less than 60 minutes for the first injection); every 3 weeks. docetaxel dose was 75mg/m2, injection on day 1;Albumin-bound Paclitaxel (no anti-allergic treatment required), 260mg/m2, injection on day 1; Cisplatin was 75mg/m2, injected on day 1.A total of two treatment cycles.
| Study group | Role | What they receive |
|---|---|---|
| Chemoradiation and pd-1 | Experimental | Subjects in Arm A receive 2 cycles of Docetaxel /Albumin-bound Paclitaxel + Cisplatin, for neoadjuvant therapy Neoadjuvant radiotherapy for 40Gy/20F Receives: Drug: Teripalimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major Pathological Response Rate (MPR)
No more than 10% of tumor cells were found in neoadjuvant surgical specimens.
Measured: 30 days after the second cycle of treatment(each cycle is 21 days)
Objective Response Rate (ORR)
Based on RECIST evaluation criteria, the proportion of patients with complete ORR was defined as the percentage of patients having a complete response or a partial response to protocol treatment. Objective response will be measured by RECIST 1.1.
Measured: At the end of cycles 2(each cycle is 21 days)
Secondary outcomes (4)
2-year Disease-Free Survival Rate (24 months DFS)
The 2-year DFS rate was defined as the rate of progression or death due to disease recurrence within 2 years
Measured: 2 years
Media Disease-free Survival (mDFS)
The time at which disease progression or death due to disease progression occurred in 50% of patients
Measured: Up to 5 years
Media overall survival (mOS)
The time of death occurred in 50% of patients
Measured: Up to 5 years
The incidence of adverse events and the incidence of severe adverse events（ grade 3-4)
Safety will be evaluated for all treated patients using CTCAE V 5.0.
Measured: 60 days after the end protocol treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2019
- Study start1 May 2019
- Primary completion30 Apr 2021 (estimated)
- Study completion30 Apr 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Esophagus CancerStudies of the same condition, open and under way.
- More trials run by Tongji 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
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tongji Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Li Zhang, MD, Principal investigator, Tongji Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04177875
- Sponsor's protocol ID
- [2019]（S910）
- Acronym
- T+TP
- Status last verified
- May 2019
- First submitted
- 30 Oct 2019
- Last updated
- 26 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Prospective, Open-label Clinical Trial of Pre-Operative PD-1 Antibody (Toripalimab) + Chemoradiotherapy in Patients With Locally Advanced Esophageal Cancer
- ClinicalTrials.gov ID
- NCT04177875
- Acronym / sponsor ID
- T+TP / [2019]（S910）
- Conditions
- Esophagus Cancer
- Keywords
- neoadjuvant therapy；pd-1 antibody combined with Chemoradiotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- Tongji HospitalUniversity, hospital or other
- Study start
- 1 May 2019 (actual)
- Primary completion
- 30 Apr 2021 (estimated)
- Study completion
- 30 Apr 2022 (estimated)
- First posted
- 26 Nov 2019 (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 study will evaluate the safety and feasibility of preoperative immune checkpoint therapy with concurrent Chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. And this study will provide valuable information for further clinical trials of preoperative Teripalimab and other immune checkpoint therapy in esophageal cancer treatment.
Detailed description
Esophageal cancer ranks the eighth most common cancer in Worldwide. And the third among men and the fifth among women in China, among which esophageal squamous cell carcinoma accounts for about 90%.
Neoadjuvant therapy for esophageal cancer is increasingly supported by evidence. However, the results of neoadjuvant therapy are not completely consistent. Most studies of neoadjuvant treatment data for esophageal cancer were obtained from western populations, where esophageal adenocarcinoma and esophagogastric junction adenocarcinoma were more common and the sample size was relatively small. According to the meta-analysis of the reported results of randomized controlled trials, concurrent chemoradiotherapy has a higher pathological complete response rate than chemotherapy alone as neoadjuvant therapy. However, the 3-year survival rate of neoadjuvant chemoradiotherapy only showed an advantage in patients with squamous cell carcinoma (56.8%vs42.8%), but no significant difference in patients with adenocarcinoma (46.3%vs41.0%). Pathological complete remission rate of esophageal cancer after neoadjuvant chemotherapy is relatively low.
It can be seen that positive expression of programmed death ligand-1 is more common in Esophageal squamous cell carcinoma, and programmed death ligand-1 tends to be overexpressed compared with adjacent normal epithelial cells. The later the T-stage of the tumor, the higher the positive expression rate. In addition, programmed death ligand-1 expression is significantly correlated with lymphatic metastasis. Therefore, programmed death ligand-1 expression can promote tumor progression. The recurrence rate of patients with programmed death ligand-1 expression is higher after treatment, and the postoperative complete pathological remission rate is lower in programmed death ligand-1 positive patients. In addition, positive programmed death ligand-1 expression also reduces the sensitivity of radiotherapy, which may be contributing factors to poor prognosis of patients with positive pd-l1 expression. It is worth mentioning that clinical treatment will affect the expression level of programmed death ligand-1 in esophageal cancer tissues. Neoadjuvant concurrent chemoradiotherapy can up-regulate the expression of programmed death ligand-1 in ESCC significantly, while neoadjuvant chemotherapy can down-regulate the expression of pd-L1. However, radiotherapy can up-regulate the expression level of programmed death ligand-1 in esophageal cancer cells, which is positively correlated with radiation dose, and the combination of anti-pd-L1 therapy and radiotherapy can lead to increased tumor cell lysis, which also indicates the importance of comprehensive treatment of tumor.
There are relatively few studies on the treatment of esophageal cancer with pd-1 / pd-L1 inhibitors. Keynote-059 enrolled 259 patients with advanced gastric or gastroesophageal junction cancer in the phase II clinical trial of Pembrolizumab, with an objective response rate of 11.6%, complete response rate of 2.3%, and median response duration of 8.4 months. Persistent objective response rates were observed in both programmed death ligand-1 positive and negative patients, and adverse reactions were tolerable.
The efficacy and safety of anti-pd-1 / pd-L1 therapy in the treatment of esophageal cancer still need a lot of clinical studies to further confirm. This study will evaluate the safety and feasibility of preoperative immune checkpoint therapy using pembrolizumab with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. And this study will provide valuable information for further clinical trials of preoperative Teripalimab and other immune checkpoint therapy in esophageal cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chemoradiation and pd-1 | Experimental | Drug: TeripalimabSubjects in Arm A receive 2 cycles of Docetaxel /Albumin-bound Paclitaxel + Cisplatin, for neoadjuvant therapy Neoadjuvant radiotherapy for 40Gy/20F |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age 18-70, male or female
- Locally advanced esophageal cancer diagnosed by pathology, Clinical tumor stage should be T2-3N0-1M0
- No previous chemoradiotherapy
- Have a performance status of 0 or 1 on the ECOG Performance Scale
- Demonstrate adequate organ function as defined below (excluding the use of any blood components and cytokines during the screening period)
Key exclusion criteria (8 listed)
- Any active autoimmune disease or history of autoimmune disease (as follows, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitritis, vasculitis, nephritis, hyperthyroidism, thyroid dysfunction);Subjects with vitiligo or who have had complete remission from childhood asthma without any intervention after adulthood may be included; Asthma requiring medical intervention with bronchodilators was not included. Those who have used other drugs in clinical trials to study drugs within 4 weeks before their first use;
- Severe allergic reaction to monoclonal antibody
- The number of neutrophils in peripheral blood was lower than 1500/mm3;
- There are clinical symptoms or diseases of the heart that are not well controlled, such as: A. heart failure above grade 2 by the Criteria of NYHA; B. unstable angina pectoris; C. myocardial infarction occurred within 1 year; D. Clinically meaningful supraventricular or ventricular arrhythmias require treatment or intervention;
- Has a previous radiotherapy, chemotherapy, hormone therapy, surgery or molecular targeted therapy;
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 |
|---|---|---|
| TeripalimabAlso: Docetaxel /Albumin-bound Paclitaxel, CisplatinTeripalimab Injection 240mg/6ml fixed dose (3mg/kg for patients weighing less than 40kg) ,injection on day 1, each infusion for 30min (no less than 60 minutes for the first injection); every 3 weeks. docetaxel dose was 75mg/m2, injection on day 1;Albumin-bound Paclitaxel (no anti-allergic treatment required), 260mg/m2, injection on day 1; Cisplatin was 75mg/m2, injected on day 1.A total of two treatment cycles. | Drug | Chemoradiation and pd-1 |
Primary outcome
Major Pathological Response Rate (MPR)
Time frame: 30 days after the second cycle of treatment(each cycle is 21 days)
No more than 10% of tumor cells were found in neoadjuvant surgical specimens.
Objective Response Rate (ORR)
Time frame: At the end of cycles 2(each cycle is 21 days)
Based on RECIST evaluation criteria, the proportion of patients with complete ORR was defined as the percentage of patients having a complete response or a partial response to protocol treatment. Objective response will be measured by RECIST 1.1.
4 secondary outcomes
2-year Disease-Free Survival Rate (24 months DFS)
Time frame: 2 years
Media Disease-free Survival (mDFS)
Time frame: Up to 5 years
Media overall survival (mOS)
Time frame: Up to 5 years
The incidence of adverse events and the incidence of severe adverse events（ grade 3-4)
Time frame: 60 days after the end protocol treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2019.
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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.
Li Zhang, MD principal investigator
Tongji 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 Teripalimab in people with Esophagus Cancer, run by Tongji 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 9 inclusion and 8 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 26 Nov 2019. 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 Li Zhang, MD (86-13554191436, luzigang@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major Pathological Response Rate (MPR) (time frame: 30 days after the second cycle of treatment(each cycle is 21 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Nov 2019.