Advanced Esophageal Squamous Cell CancerPhase 2NCT04437212
Neoadjuvant Chemoradiotherapy Combined With Perioperative Toripalimab in Locally Advanced Esophageal Cancer
A Phase 2 study testing Toripalimab in people with Advanced Esophageal Squamous Cell Cancer, run by RenJi Hospital at 1 site in China.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced Esophageal Squamous Cell Cancer
- What is being tested?
- Toripalimab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2020to 31 Dec 2023
- 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
- Aged 18 to 75 years old of either gender
- Patients with histopathological confirmed resectable thoracic esophageal squamous cell carcinoma who are anti-tumor treatment-naive;
- Clinical stage of T1-4aN1-2M0 or T3-4aN0M0 according to the 8th edition of the UICC staging system;
- ECOG PS score of 0-1;
- The indexes of hematology, biochemistry and organ function meet the following requirements: a. white blood cell count (WBC) ≥ 3.0×109/L；b. neutrophil count (ANC) ≥ 1.5×109/L; c. platelets ≥ 85×109/L; d. hemoglobin ≥ 9g/dL; e. total bilirubin ≤ 14.4µmol/L; f. ALT ≤ 75U/L; g. serum creatinine ≤ 104µmol/L and creatinine clearance rate >60 mL/min;
- Women of childbearing age must undergo a pregnancy test within 7 days before enrolling in the treatment, and those who are negative can be enrolled. Patients of childbearing age and their sexual partners agree to use reliable methods of contraception before entering the study, during the study, and at least 180 days after the end of the study;
- Ability to understand the study and sign informed consent.
Who cannot join
- Patients with active infection within 2 weeks before the first use of the study drug or need to be treated with oral or intravenous antibiotics;
- A history of interstitial lung disease or non-infectious pneumonia;
- Patients whose clinician judges surgery as the first choice for the best treatment;
- A history of autoimmune diseases or abnormal immune system ;
- Patients who cannot tolerate chemoradiotherapy or surgery due to severe cardiac, lung dysfunction。
- Patients diagnosed with any other malignant tumor within 5 years before enrollment, except for malignant tumors with low risk of recurrence and risk of death, such as fully treated basal cell or squamous cell skin and carcinoma in situ of the cervix;
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- Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of Toripalimab, and the chemotherapeutic drugs paclitaxel or cisplatin;
- A history of immunodeficiency，including a positive HIV test result or other acquired or congenital immunodeficiency diseases, a history of organ transplantation or allogeneic bone marrow transplantation;
- Women during pregnancy or lactation;
- Other situations not suitable for enrollment.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Renji Hospital
Shanghai, Shanghai Municipality, 200127
Xiumei Ma, doctor, 86-21-68383624, sallyma@hotmail.com
Xiumei Ma, doctor
About this study
Official title: A Phase II Prospective, Open-label Clinical Trial of Neoadjuvant Chemoradiotherapy Combined With Perioperative Toripalimab in Patients With Locally Advanced Esophageal Squamous Cell Cancer
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 PD-1/PD-L1 checkpoints has demonstrated promising activity in advanced EC especially 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.
The aim of this study was to evaluate the efficacy and safety of the neoadjuvant chemoradiotherapy combined with perioperative toripalimab in patients with locally advanced esophageal squamous cell cancer.
- Conditions
- Advanced Esophageal Squamous Cell Cancer
- Being tested
- Toripalimab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ToripalimabDrug
Also called JS-001
Patients received toripalimab 240mg every 3 weeks 1-7 days after neoadjuvant chemoradiotherapy for 2 cycles before operation and 28-42 days after operation for 4 cycles.
| Study group | Role | What they receive |
|---|---|---|
| Toripalimab Group | Experimental | All patients will receive radiation therapy scheme: 41.4Gy in 23 fractions over 5 weeks, concurrently with 5 cycles of paclitaxel/cisplatin (paclitaxel 45mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22,29 and 2 cycles of toripalimab 240 mg every 3 weeks after chemoradiotherapy. Esophagectomy is performed 6-8 weeks after CRT completion and after operation patients received 4 cycles of toripalimab 240 mg every 3 weeks for adjuvant treatment. Receives: Drug: Toripalimab |
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: From date of surgery to 14 days later
Secondary outcomes (4)
2-year disease-free survival
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.
2-year overall survival
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
Incidence of Treatment-related Adverse Events as Assessed by CTCAE v5.0
Measured: 60 days after the end protocol treatment
Perioperative complication rate
Measured: From date of surgery to 30 days later
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2020
- Study start1 Jul 2020 (estimated)
- Primary completion31 Dec 2021 (estimated)
- Study completion31 Dec 2023 (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 Advanced Esophageal Squamous Cell CancerStudies of the same condition, open and under way.
- More trials run by RenJi 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
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RenJi Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Xiumei Ma, doctor, Principal investigator, RenJi Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04437212
- Sponsor's protocol ID
- Renji-KY2019-174
- Status last verified
- Jun 2020
- First submitted
- 16 Jun 2020
- Last updated
- 26 Jun 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Xu X, Sun Z, Liu Q, Zhang Y, Shen L, Zhang C, Lin H, Hu B, Rong L, Chen H, Wang X, Zhao X, Bai YR, Ye Q, Ma X. Neoadjuvant chemoradiotherapy combined with sequential perioperative toripalimab in locally advanced esophageal squamous cell cancer. J Immunother Cancer. 2024 Mar 7;12(3):e008631. doi: 10.1136/jitc-2023-008631.
PubMed 38458635
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Prospective, Open-label Clinical Trial of Neoadjuvant Chemoradiotherapy Combined With Perioperative Toripalimab in Patients With Locally Advanced Esophageal Squamous Cell Cancer
- ClinicalTrials.gov ID
- NCT04437212
- Acronym / sponsor ID
- Renji-KY2019-174
- Conditions
- Advanced Esophageal Squamous Cell Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- RenJi HospitalUniversity, hospital or other
- Study start
- 1 Jul 2020 (estimated)
- Primary completion
- 31 Dec 2021 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 18 Jun 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.
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 PD-1/PD-L1 checkpoints has demonstrated promising activity in advanced EC especially 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.
The aim of this study was to evaluate the efficacy and safety of the neoadjuvant chemoradiotherapy combined with perioperative toripalimab in patients with locally advanced esophageal squamous cell cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Toripalimab Group | Experimental | Drug: ToripalimabAll patients will receive radiation therapy scheme: 41.4Gy in 23 fractions over 5 weeks, concurrently with 5 cycles of paclitaxel/cisplatin (paclitaxel 45mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22,29 and 2 cycles of toripalimab 240 mg every 3 weeks after chemoradiotherapy. Esophagectomy is performed 6-8 weeks after CRT completion and after operation patients received 4 cycles of toripalimab 240 mg every 3 weeks for adjuvant treatment. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Aged 18 to 75 years old of either gender
- Patients with histopathological confirmed resectable thoracic esophageal squamous cell carcinoma who are anti-tumor treatment-naive;
- Clinical stage of T1-4aN1-2M0 or T3-4aN0M0 according to the 8th edition of the UICC staging system;
- ECOG PS score of 0-1;
- The indexes of hematology, biochemistry and organ function meet the following requirements: a. white blood cell count (WBC) ≥ 3.0×109/L；b. neutrophil count (ANC) ≥ 1.5×109/L; c. platelets ≥ 85×109/L; d. hemoglobin ≥ 9g/dL; e. total bilirubin ≤ 14.4µmol/L; f. ALT ≤ 75U/L; g. serum creatinine ≤ 104µmol/L and creatinine clearance rate >60 mL/min;
Key exclusion criteria (10 listed)
- Patients with active infection within 2 weeks before the first use of the study drug or need to be treated with oral or intravenous antibiotics;
- A history of interstitial lung disease or non-infectious pneumonia;
- Patients whose clinician judges surgery as the first choice for the best treatment;
- A history of autoimmune diseases or abnormal immune system ;
- Patients who cannot tolerate chemoradiotherapy or surgery due to severe cardiac, lung dysfunction。
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-001Patients received toripalimab 240mg every 3 weeks 1-7 days after neoadjuvant chemoradiotherapy for 2 cycles before operation and 28-42 days after operation for 4 cycles. | Drug | Toripalimab Group |
Primary outcome
Major Pathological Response Rate (MPR)
Time frame: From date of surgery to 14 days later
No more than 10% of tumor cells were found in neoadjuvant surgical specimens.
4 secondary outcomes
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.
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
Incidence of Treatment-related Adverse Events as Assessed by CTCAE v5.0
Time frame: 60 days after the end protocol treatment
Perioperative complication rate
Time frame: From date of surgery to 30 days later
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2020.
- Derived from this study: PubMed 38458635Xu X, Sun Z, Liu Q, Zhang Y, Shen L, Zhang C, Lin H, Hu B, Rong L, Chen H, Wang X, Zhao X, Bai YR, Ye Q, Ma X. Neoadjuvant chemoradiotherapy combined with sequential perioperative toripalimab in locally advanced esophageal squamous cell cancer. J Immunother Cancer. 2024 Mar 7;12(3):e008631. doi: 10.1136/jitc-2023-008631.
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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.
Xiumei Ma, doctor principal investigator
RenJi 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 Toripalimab in people with Advanced Esophageal Squamous Cell Cancer, run by RenJi 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 7 inclusion and 10 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 Jun 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 Xiumei Ma, doctor (86-21-68683624, sallyma@hotmail.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: From date of surgery to 14 days later). 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 NCT04437212, 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 26 Jun 2020.