Esophageal Squamous Cell CarcinomaPhase 2NCT04644250
Combination of Toripalimab and Neoadjuvant Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma
A Phase 2 study testing Toripalimab, Paclitaxel liposome/Carboplatin and Intensity-modulated radiotherapy in people with Esophageal Squamous Cell Carcinoma, run by Wei Ren at 1 site in China.
Trial summary
Radical resection is thought to be the mainstay of esophageal cancer treatment. Neoadjuvant chemoradiotherapy (CRT) followed by surgery has become the standard treatment option for locally advanced esophageal squamous cell cancer (ESCC). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Esophageal Squamous Cell Carcinoma
- What is being tested?
- Toripalimab, Paclitaxel liposome/Carboplatin and Intensity-modulated radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2020to 1 Mar 2024
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18 to 70 years old of either gender
- A histopathological diagnosis of resectable thoracic esophageal squamous cell carcinoma(The midpoint of the upper and lower margins of the primary tumor is ≥25cm from the incisor)
- There is no distant metastasis and the esophageal tumor can be resected or potentially resectable after the expert consultation of thoracic surgery. The clinical stage is cT3-4aN0-2M0, patients with stage Ⅱ, Ⅲ, and IVA (AJCC 8th edition cTNM staging);
- ECOG PS score of 0-1;
- Patients who are anti-tumor treatment-naive;
- Estimated life expectancy >6 months
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- Baseline the function of important organs meets the following requirements: a. white blood cell count (WBC) ≥ 3×109/L, absolute neutrophil count (ANC) ≥ 1.5×109/L，;Baseline organ function meets: ①WBC≥3×109/L, ANC≥1.5×109/L, PLT≥100×109/L, Hb≥90g/L; ②Liver function: TBIL≤2ULN, Aspartate aminotransferase（AST） ≤2.5ULN, ALT≤2.5ULN ③renal function: cCr≥60 ml/min, Cr≤1.5 ULN; ④heart function: no heart disease or coronary heart disease, the patient's heart function is 1-2 grade;
- The blood pressure of hypertensive patients should be controlled within the normal range with antihypertensive drugs;
- The fasting blood-glucose of diabetic patients should be controlled at ≤8mmol/L through hypoglycemic drugs;
- No other serious diseases that conflict with this plan (such as autoimmune diseases, immunodeficiency, organ transplantation, or other diseases that require continuous hormone therapy);
- No history of other malignant tumors;
- The patient agrees to participate in this clinical study and signs the "Informed Consent". Ability to understand the study and sign informed consent.
Who cannot join
- Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.);
- Patients with other malignant tumors (non-malignant black skin tumors, cervical cancer in situ, except for cured prostate cancer);
- Patients who have been or expected to have a significant risk of esophageal perforation, fistula, and major bleeding;
- Patients who have active autoimmune diseases or patients who are undergoing treatment of autoimmune diseases (Prior therapy with immunosuppressant, the dose of immunosuppressant used ≥10mg/day, oral prednisone for more than 2 weeks);.
- Uncontrolled clinically significant cardiovascular and cerebrovascular diseases , including but not limited to severe acute myocardial infarction, unstable or severe angina pectoris, coronary artery bypass surgery, congestive heart failure, ventricular arrhythmia requiring medical intervention within 6 months before enrollment 、Left ventricular ejection fraction <50%, or other patients who are not expected to tolerate chemotherapy and radiotherapy;Cardiac clinical symptoms or diseases that are not well controlled, such as: a. Heart Failure（New York Heart Association）> Class Ⅱ, b. unstable angina, c. myocardial infarction within 1 year; d. Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.
- Patients who were severe allergic constitution;;
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- Patients who were pregnant or lactating women;
- Patients who have severe mental disorders;
- Patients who have peripheral nerve disease with common terminology criteria (CTC）grade ≥3;
- Abnormal blood coagulation function including PT>16s, activated partial thromboplastin time（APTT）>53s, Thrombin time（TT）>21s, Fib<1.5g/L, bleeding tendency or receiving thrombolytic or anticoagulant therapy;
- Patients who hsve severe pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, severely impaired lung function, etc past or present., or active tuberculosis within 1 year;
- Patients who have active hepatitis B or C;
- Patients who did not meet the enrollment conditions xia researchers evaluated.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Nanjing Drum Tower Hospital
Nanjing, Jiangsu, 210000
Wei Ren, 13915981834, renwei@njglyy.com
About this study
Official title: Phase II of Toripalimab Chemoradiotherapy in Neoadjuvant Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma: A Single-center、Open Lable、Single-arm Exploratory Clinical Research
Radical resection is thought to be the mainstay of esophageal cancer treatment. Neoadjuvant chemoradiotherapy (CRT) followed by surgery has become the standard treatment option for locally advanced esophageal squamous cell cancer (ESCC). However, only 20% to 40% of patients can achieve pathologic complete response (pCR) after neoadjuvant CRT with favorable prognosis and about 10% of patients have disease progression after chemoradiotherapy. How to improve the the efficacy of neoadjuvant therapy is an important clinical problem to be solved.
Immunotherapy targeting the programmed cell death receptor-1（PD-1） /programmed cell death-Ligand 1(PD-L1) checkpoints has demonstrated promising activity in ESCC. In Keynote181 study, for patients with metastatic esophageal squamous cell carcinoma, regardless of PD-L1 expression, pembrolizumab significantly improved overall survival compared with chemotherapy. However, the efficacy and safety of immunotherapy therapy in surgery-based multidisciplinary treatment of local advanced esophageal cancer still need a lot of clinical studies to further confirm.
This study aims to investigate the safety and efficacy of Toripalimab combined with radiotherapy and chemotherapy in neoadjuvant treatment of locally advanced esophageal squamous cell carcinoma
Read the detailed description
This study was designed as an open-lable, single-arm, single-center,exploratory clinical study. Toripalimab combination of chemoradiotherapy as neoadjuvant therapy. Participants will receive carboplatin (AUC=2) and paclitaxel liposome (50mg/m²) on day 3,10,17,24,31. And radiotherapy Intensity-modulated radiation therapy（IMRT）will start from day 1 to 31 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy. Participants will also receive Toripalimab (240mg) on days 3, 24and 45. After the neoadjuvant treatment is over, the short-term efficacy evaluation will be performed first, and then a radical resection will be scheduled on Day 59 to 73. This study include 2 phases: 14 cases were enrolled in the first stage and 18 cases were enrolled in the second stage.
- Conditions
- Esophageal Squamous Cell Carcinoma
- Being tested
- Toripalimab, Paclitaxel liposome/Carboplatin, Intensity-modulated radiotherapy
- Keywords
- Locally advanced esophageal squamous cell carcinoma, Neoadjuvant chemoradiotherapy, Radical resection, Toripalimab
- 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.
ToripalimabDrug
Also called JS-001
Participants will also receive Toripalimab(240mg) VD 30 min on days 3, 24 and 45，3 cycles in total.
Paclitaxel liposome/CarboplatinDrug
Also called PCb
Participants will receive carboplatin (AUC=2) VD 30min and paclitaxel liposome (50mg/m²) CIV 24h on day 3,10,17,24,31, 5cycles in total.
Intensity-modulated radiotherapyRadiation
Also called IMRT
A total of 41.4 Gy, 23 fractions of 1.8 Gy on Day 1 to 31.
| Study group | Role | What they receive |
|---|---|---|
| Arm1 | Experimental | Arm1:preoperative Toripalimab with chemoradiotherapy group Participants will receive carboplatin (AUC=2) VD 30min and paclitaxel liposome (50mg/m²) CIV 24h on day 3,10,17,24,31. And radiotherapy will start from day 1 to 31 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy. Participants will also receive Toripalimab(240mg) VD 30 min on days 3, 24 and 45. After the above neoadjuvant therapy is over, the short-term efficacy evaluation will be performed first, and then a scheduled radical radical resection will be performed from days 59 to 73. Receives: Drug: Toripalimab; Drug: Paclitaxel liposome/Carboplatin; Radiation: Intensity-modulated radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic complete response rate
Pathologic complete response was defined as pT0N0M0（clinical stage). The rate of pathologic complete response rate after neoadjuvant chemoradiotherapy.
Measured: Three working days after surgery
Secondary outcomes (6)
Incidence of Treatment-related Adverse Events as Assessed by CTCAE v4.0
The neoadjuvant treatment-related adverse events
Measured: From the enrollment to the date of surgery
2-year overall survival
The 2-year overall survival of the whole group
Measured: From 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
2-year disease-free survival
The 2-year disease-free survival of the whole group
Measured: From date of surgery until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months.
Major Pathological Response (MPR) rate
MPR is defined as 10% or fewer viable cancer cells in the hematoxylin and eosin (H\&E)-stained slides from the resected tumor following neoadjuvant treatment.
Measured: From date of surgery to 14 days later
Objective Response Rate (ORR)
Objective response rate is defined as the rate of patients with at least a 30% decrease in the sum of the longest diameter of target lesions, which include complete response (CR) or partial response (PR).
Measured: At the end of Cycle 2 (each cycle is 21 days)
R0 resection rate
The R0 resection rate of esophagectomy
Measured: Three working days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2020
- Study start1 Sep 2020
- Primary completion1 Mar 2022 (estimated)
- Study completion1 Mar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Esophageal Squamous Cell CarcinomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wei Ren
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Wei Ren, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04644250
- Sponsor's protocol ID
- GLYY-EC-NAD-01
- Status last verified
- Nov 2020
- First submitted
- 16 Nov 2020
- Last updated
- 25 Nov 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II of Toripalimab Chemoradiotherapy in Neoadjuvant Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma: A Single-center、Open Lable、Single-arm Exploratory Clinical Research
- ClinicalTrials.gov ID
- NCT04644250
- Acronym / sponsor ID
- GLYY-EC-NAD-01
- Conditions
- Esophageal Squamous Cell Carcinoma
- Keywords
- Locally advanced esophageal squamous cell carcinoma, Neoadjuvant chemoradiotherapy, Radical resection, Toripalimab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Wei RenUniversity, hospital or other
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- 1 Mar 2022 (estimated)
- Study completion
- 1 Mar 2024 (estimated)
- First posted
- 25 Nov 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.
Radical resection is thought to be the mainstay of esophageal cancer treatment. Neoadjuvant chemoradiotherapy (CRT) followed by surgery has become the standard treatment option for locally advanced esophageal squamous cell cancer (ESCC). However, only 20% to 40% of patients can achieve pathologic complete response (pCR) after neoadjuvant CRT with favorable prognosis and about 10% of patients have disease progression after chemoradiotherapy. How to improve the the efficacy of neoadjuvant therapy is an important clinical problem to be solved.
Immunotherapy targeting the programmed cell death receptor-1（PD-1） /programmed cell death-Ligand 1(PD-L1) checkpoints has demonstrated promising activity in ESCC. In Keynote181 study, for patients with metastatic esophageal squamous cell carcinoma, regardless of PD-L1 expression, pembrolizumab significantly improved overall survival compared with chemotherapy. However, the efficacy and safety of immunotherapy therapy in surgery-based multidisciplinary treatment of local advanced esophageal cancer still need a lot of clinical studies to further confirm.
This study aims to investigate the safety and efficacy of Toripalimab combined with radiotherapy and chemotherapy in neoadjuvant treatment of locally advanced esophageal squamous cell carcinoma
Detailed description
This study was designed as an open-lable, single-arm, single-center,exploratory clinical study. Toripalimab combination of chemoradiotherapy as neoadjuvant therapy. Participants will receive carboplatin (AUC=2) and paclitaxel liposome (50mg/m²) on day 3,10,17,24,31. And radiotherapy Intensity-modulated radiation therapy（IMRT）will start from day 1 to 31 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy. Participants will also receive Toripalimab (240mg) on days 3, 24and 45. After the neoadjuvant treatment is over, the short-term efficacy evaluation will be performed first, and then a radical resection will be scheduled on Day 59 to 73. This study include 2 phases: 14 cases were enrolled in the first stage and 18 cases were enrolled in the second stage.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm1 | Experimental | Drug: Toripalimab, Drug: Paclitaxel liposome/Carboplatin, Radiation: Intensity-modulated radiotherapyArm1:preoperative Toripalimab with chemoradiotherapy group Participants will receive carboplatin (AUC=2) VD 30min and paclitaxel liposome (50mg/m²) CIV 24h on day 3,10,17,24,31. And radiotherapy will start from day 1 to 31 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy. Participants will also receive Toripalimab(240mg) VD 30 min on days 3, 24 and 45. After the above neoadjuvant therapy is over, the short-term efficacy evaluation will be performed first, and then a scheduled radical radical resection will be performed from days 59 to 73. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Aged 18 to 70 years old of either gender
- A histopathological diagnosis of resectable thoracic esophageal squamous cell carcinoma(The midpoint of the upper and lower margins of the primary tumor is ≥25cm from the incisor)
- There is no distant metastasis and the esophageal tumor can be resected or potentially resectable after the expert consultation of thoracic surgery. The clinical stage is cT3-4aN0-2M0, patients with stage Ⅱ, Ⅲ, and IVA (AJCC 8th edition cTNM staging);
- ECOG PS score of 0-1;
- Patients who are anti-tumor treatment-naive;
Key exclusion criteria (13 listed)
- Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.);
- Patients with other malignant tumors (non-malignant black skin tumors, cervical cancer in situ, except for cured prostate cancer);
- Patients who have been or expected to have a significant risk of esophageal perforation, fistula, and major bleeding;
- Patients who have active autoimmune diseases or patients who are undergoing treatment of autoimmune diseases (Prior therapy with immunosuppressant, the dose of immunosuppressant used ≥10mg/day, oral prednisone for more than 2 weeks);.
- Uncontrolled clinically significant cardiovascular and cerebrovascular diseases , including but not limited to severe acute myocardial infarction, unstable or severe angina pectoris, coronary artery bypass surgery, congestive heart failure, ventricular arrhythmia requiring medical intervention within 6 months before enrollment 、Left ventricular ejection fraction <50%, or other patients who are not expected to tolerate chemotherapy and radiotherapy;Cardiac clinical symptoms or diseases that are not well controlled, such as: a. Heart Failure（New York Heart Association）> Class Ⅱ, b. unstable angina, c. myocardial infarction within 1 year; d. Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.
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 |
|---|---|---|
| ToripalimabAlso: JS-001Participants will also receive Toripalimab(240mg) VD 30 min on days 3, 24 and 45，3 cycles in total. | Drug | Arm1 |
| Paclitaxel liposome/CarboplatinAlso: PCbParticipants will receive carboplatin (AUC=2) VD 30min and paclitaxel liposome (50mg/m²) CIV 24h on day 3,10,17,24,31, 5cycles in total. | Drug | Arm1 |
| Intensity-modulated radiotherapyAlso: IMRTA total of 41.4 Gy, 23 fractions of 1.8 Gy on Day 1 to 31. | Radiation | Arm1 |
Primary outcome
Pathologic complete response rate
Time frame: Three working days after surgery
Pathologic complete response was defined as pT0N0M0（clinical stage). The rate of pathologic complete response rate after neoadjuvant chemoradiotherapy.
6 secondary outcomes
Incidence of Treatment-related Adverse Events as Assessed by CTCAE v4.0
Time frame: From the enrollment to the date of surgery
2-year overall survival
Time frame: From 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
2-year disease-free survival
Time frame: From date of surgery until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months.
Major Pathological Response (MPR) rate
Time frame: From date of surgery to 14 days later
Objective Response Rate (ORR)
Time frame: At the end of Cycle 2 (each cycle is 21 days)
R0 resection rate
Time frame: Three working days after surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2020.
- Individual participant dataSharing planned: No
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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.
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 Toripalimab, Paclitaxel liposome/Carboplatin and Intensity-modulated radiotherapy in people with Esophageal Squamous Cell Carcinoma, run by Wei Ren 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 12 inclusion and 13 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 25 Nov 2020. 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 Wei Ren (13915981834, renwei@njglyy.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic complete response rate (time frame: Three working days after surgery). 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 25 Nov 2020.