Unresectable Esophageal CancerPhase 2NCT04005170
Combination of Toripalimab and Chemoradiotherapy in Esophageal Cancer
A Phase 2 study testing Toripalimab, Paclitaxel/Cisplatin and Intensity-modulated radiotherapy in people with Unresectable Esophageal Cancer, run by Mian XI at 1 site in China.
Trial summary
Definitive chemoradiotherapy (CRT) is the standard treatment option for unresectable esophageal cancer (EC). However, as high as more than 40% of EC patients experienced locoregional recurrence after concurrent CRT. Immunotherapy targeting the PD-1/PD-L1 checkpoints has demonstrated promising activity in advanced EC. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Unresectable Esophageal Cancer
- What is being tested?
- Toripalimab, Paclitaxel/Cisplatin and Intensity-modulated radiotherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteChina
- Study dates
- 25 Jun 2019to 31 Jul 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed squamous cell carcinoma of the esophagus;
- Absence of hematogenous metastasis disease, confirmed by endoscopic ultrasound (EUS) and PET-CT scan (according to UICC TNM version 8);
- Not suitable for surgery (either for medical reasons or patient's choice);
- Age at diagnosis 18 to 70 years;
- No prior cancer therapy;
- Estimated life expectancy >6 months;
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- Eastern Cooperative Oncology Group performance status ≤ 2
- No history of concomitant or previous malignancy;
- The function of important organs meets the following requirements: a. white blood cell count (WBC) ≥ 4.0×109/L, absolute neutrophil count (ANC) ≥ 1.5×109/L; b. platelets ≥ 100×109/L; c. hemoglobin ≥ 9g/dL; d. serum albumin ≥ 2.8g/dL; e. total bilirubin ≤ 1.5×ULN, ALT, AST and/or AKP ≤ 2.5×ULN; f. serum creatinine ≤ 1.5×ULN or creatinine clearance rate >60 mL/min;
- 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 hematogenous metastasis disease at diagnosis;
- Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of Toripalimab, and the chemotherapeutic drugs paclitaxel or cisplatin;
- Patients who have a preexisting or coexisting bleeding disorder;
- Female patients who are pregnant or lactating;
- Inability to provide informed consent due to psychological, familial, social and other factors;
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- Presence of CTC grade ≥ 3 peripheral neuropathy;
- A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer
- A history of diabetes for more than 10 years and poorly controlled blood glucose levels;
- Patients who cannot tolerate chemoradiotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia.
- Active autoimmune diseases, a history of autoimmune diseases (including but not limited to these diseases or syndromes, such as colitis, hepatitis, hyperthyroidism), 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;
- A history of interstitial lung disease or non-infectious pneumonia;
- 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;
- Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C hepatitis C antibody, and HCV-RNA levels higher than the lower limit of the assay).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Trial of Combination of Toripalimab and Definitive Chemoradiotherapy in Esophageal Squamous Cell Carcinoma
Definitive chemoradiotherapy (CRT) is the standard treatment option for unresectable esophageal cancer (EC). However, as high as more than 40% of EC patients experienced locoregional recurrence after concurrent CRT. Immunotherapy targeting the PD-1/PD-L1 checkpoints has demonstrated promising activity in advanced EC. The aim of this study was to evaluate the efficacy and safety of the combination of toripalimab (an anti-PD-1 antibody) combined with definitive CRT in locally advanced esophageal squamous cell carcinoma (ESCC).
- Conditions
- Unresectable Esophageal Cancer
- Being tested
- Toripalimab, Paclitaxel/Cisplatin, Intensity-modulated radiotherapy
- Keywords
- Esophageal squamous cell carcinoma, Definitive chemoradiotherapy, Toripalimab, Clinical complete response
- 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
Patients received toripalimab 240 mg on days 1 and 22 during radiotherapy followed by a maintenance phase of toripalimab IV 240 mg every 3 weeks for up to 1 year.
Paclitaxel/CisplatinDrug
Also called TP
Patients received 5 cycles of paclitaxel/cisplatin (paclitaxel 50mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22, 29 during radiotherapy.
Intensity-modulated radiotherapyRadiation
Also called IMRT
All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is 50.4 Gy in 28 fractions over 5-6 weeks.
| Study group | Role | What they receive |
|---|---|---|
| PD-1 group | Experimental | All patients will receive standard fractionation radiation therapy (RT) scheme: 50.4 Gy in 28 fractions over 5-6 weeks, concurrently with 5 cycles of paclitaxel/cisplatin (paclitaxel 50mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22, 29 and 2 cycles of toripalimab 240 mg on days 1, 22 followed by a maintenance phase of toripalimab IV 240 mg every 3 weeks for up to 1 year. Receives: Drug: Toripalimab; Drug: Paclitaxel/Cisplatin; Radiation: Intensity-modulated radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
clinical complete response rate
Tumor response was evaluated 3 months after the completion of chemoradiotherapy based on CT or PET-CT scans, endoscopy with biopsies.
Measured: 3 months after chemoradiotherapy (plus or minus 14 days)
Secondary outcomes (4)
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 progression-free survival
The 2-year progression-free survival of the whole group
Measured: From 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
Duration of response
Tumor response was evaluated every two months after chemoradiotherapy according to RECIST criteria
Measured: From date of first CR/PR to the date of first PD according to RECIST criteria, assessed up to 24 months
Incidence of treatment-related adverse events as assessed by CTCAE v4.0
Toxicity of treatment was evaluated according to CTCAE 4.0
Measured: From the start of treatment to 2 year after the completion of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2019
- Study start25 Jun 2019
- Primary completion31 Dec 2020
- Study completion31 Jul 2022
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 Unresectable 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mian XI
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Mian XI, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04005170
- Sponsor's protocol ID
- TORIDEFEC
- Status last verified
- Aug 2022
- First submitted
- 26 Jun 2019
- Last updated
- 23 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fu J, Wang F, Dong LH, Zhang J, Deng CL, Wang XL, Xie XY, Zhang J, Deng RX, Zhang LB, Wu H, Feng H, Chen B, Song HF. Preclinical evaluation of the efficacy, pharmacokinetics and immunogenicity of JS-001, a programmed cell death protein-1 (PD-1) monoclonal antibody. Acta Pharmacol Sin. 2017 May;38(5):710-718. doi: 10.1038/aps.2016.161. Epub 2017 Mar 20.
PubMed 28317872Tang B, Yan X, Sheng X, Si L, Cui C, Kong Y, Mao L, Lian B, Bai X, Wang X, Li S, Zhou L, Yu J, Dai J, Wang K, Hu J, Dong L, Song H, Wu H, Feng H, Yao S, Chi Z, Guo J. Safety and clinical activity with an anti-PD-1 antibody JS001 in advanced melanoma or urologic cancer patients. J Hematol Oncol. 2019 Jan 14;12(1):7. doi: 10.1186/s13045-018-0693-2.
PubMed 30642373Zhou S, Zhao L, Liang Z, Liu S, Li Y, Liu S, Yang H, Liu M, Xi M. Indoleamine 2,3-dioxygenase 1 and Programmed Cell Death-ligand 1 Co-expression Predicts Poor Pathologic Response and Recurrence in Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy. Cancers (Basel). 2019 Feb 1;11(2):169. doi: 10.3390/cancers11020169.
PubMed 30717285Wang R, Ling Y, Chen B, Zhu Y, Hu Y, Liu M, Yang Y, Zhang L, Lv Y, Liu S, Li Q, Xi M. Long-term survival and post-hoc analysis of toripalimab plus definitive chemoradiotherapy for oesophageal squamous cell carcinoma: insights from the EC-CRT-001 phase II trial. EClinicalMedicine. 2024 Aug 30;75:102806. doi: 10.1016/j.eclinm.2024.102806. eCollection 2024 Sep.
PubMed 39281099Zhu Y, Wen J, Li Q, Chen B, Zhao L, Liu S, Yang Y, Wang S, Lv Y, Li J, Zhang L, Hu Y, Liu M, Xi M. Toripalimab combined with definitive chemoradiotherapy in locally advanced oesophageal squamous cell carcinoma (EC-CRT-001): a single-arm, phase 2 trial. Lancet Oncol. 2023 Apr;24(4):371-382. doi: 10.1016/S1470-2045(23)00060-8.
PubMed 36990609
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Combination of Toripalimab and Definitive Chemoradiotherapy in Esophageal Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT04005170
- Acronym / sponsor ID
- TORIDEFEC
- Conditions
- Unresectable Esophageal Cancer
- Keywords
- Esophageal squamous cell carcinoma, Definitive chemoradiotherapy, Toripalimab, Clinical complete response
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Mian XIUniversity, hospital or other
- Study start
- 25 Jun 2019 (actual)
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 31 Jul 2022 (actual)
- First posted
- 2 Jul 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.
Definitive chemoradiotherapy (CRT) is the standard treatment option for unresectable esophageal cancer (EC). However, as high as more than 40% of EC patients experienced locoregional recurrence after concurrent CRT. Immunotherapy targeting the PD-1/PD-L1 checkpoints has demonstrated promising activity in advanced EC. The aim of this study was to evaluate the efficacy and safety of the combination of toripalimab (an anti-PD-1 antibody) combined with definitive CRT in locally advanced esophageal squamous cell carcinoma (ESCC).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PD-1 group | Experimental | Drug: Toripalimab, Drug: Paclitaxel/Cisplatin, Radiation: Intensity-modulated radiotherapyAll patients will receive standard fractionation radiation therapy (RT) scheme: 50.4 Gy in 28 fractions over 5-6 weeks, concurrently with 5 cycles of paclitaxel/cisplatin (paclitaxel 50mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22, 29 and 2 cycles of toripalimab 240 mg on days 1, 22 followed by a maintenance phase of toripalimab IV 240 mg every 3 weeks for up to 1 year. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histologically confirmed squamous cell carcinoma of the esophagus;
- Absence of hematogenous metastasis disease, confirmed by endoscopic ultrasound (EUS) and PET-CT scan (according to UICC TNM version 8);
- Not suitable for surgery (either for medical reasons or patient's choice);
- Age at diagnosis 18 to 70 years;
- No prior cancer therapy;
Key exclusion criteria (14 listed)
- Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.);
- Patients with hematogenous metastasis disease at diagnosis;
- Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of Toripalimab, and the chemotherapeutic drugs paclitaxel or cisplatin;
- Patients who have a preexisting or coexisting bleeding disorder;
- Female patients who are pregnant or lactating;
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 240 mg on days 1 and 22 during radiotherapy followed by a maintenance phase of toripalimab IV 240 mg every 3 weeks for up to 1 year. | Drug | PD-1 group |
| Paclitaxel/CisplatinAlso: TPPatients received 5 cycles of paclitaxel/cisplatin (paclitaxel 50mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22, 29 during radiotherapy. | Drug | PD-1 group |
| Intensity-modulated radiotherapyAlso: IMRTAll patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is 50.4 Gy in 28 fractions over 5-6 weeks. | Radiation | PD-1 group |
Primary outcome
clinical complete response rate
Time frame: 3 months after chemoradiotherapy (plus or minus 14 days)
Tumor response was evaluated 3 months after the completion of chemoradiotherapy based on CT or PET-CT scans, endoscopy with biopsies.
4 secondary outcomes
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 progression-free survival
Time frame: From 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
Duration of response
Time frame: From date of first CR/PR to the date of first PD according to RECIST criteria, assessed up to 24 months
Incidence of treatment-related adverse events as assessed by CTCAE v4.0
Time frame: From the start of treatment to 2 year after the completion of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2022.
- Background: PubMed 28317872Fu J, Wang F, Dong LH, Zhang J, Deng CL, Wang XL, Xie XY, Zhang J, Deng RX, Zhang LB, Wu H, Feng H, Chen B, Song HF. Preclinical evaluation of the efficacy, pharmacokinetics and immunogenicity of JS-001, a programmed cell death protein-1 (PD-1) monoclonal antibody. Acta Pharmacol Sin. 2017 May;38(5):710-718. doi: 10.1038/aps.2016.161. Epub 2017 Mar 20.
- Background: PubMed 30642373Tang B, Yan X, Sheng X, Si L, Cui C, Kong Y, Mao L, Lian B, Bai X, Wang X, Li S, Zhou L, Yu J, Dai J, Wang K, Hu J, Dong L, Song H, Wu H, Feng H, Yao S, Chi Z, Guo J. Safety and clinical activity with an anti-PD-1 antibody JS001 in advanced melanoma or urologic cancer patients. J Hematol Oncol. 2019 Jan 14;12(1):7. doi: 10.1186/s13045-018-0693-2.
- Background: PubMed 30717285Zhou S, Zhao L, Liang Z, Liu S, Li Y, Liu S, Yang H, Liu M, Xi M. Indoleamine 2,3-dioxygenase 1 and Programmed Cell Death-ligand 1 Co-expression Predicts Poor Pathologic Response and Recurrence in Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy. Cancers (Basel). 2019 Feb 1;11(2):169. doi: 10.3390/cancers11020169.
- Derived from this study: PubMed 39281099Wang R, Ling Y, Chen B, Zhu Y, Hu Y, Liu M, Yang Y, Zhang L, Lv Y, Liu S, Li Q, Xi M. Long-term survival and post-hoc analysis of toripalimab plus definitive chemoradiotherapy for oesophageal squamous cell carcinoma: insights from the EC-CRT-001 phase II trial. EClinicalMedicine. 2024 Aug 30;75:102806. doi: 10.1016/j.eclinm.2024.102806. eCollection 2024 Sep.
- Derived from this study: PubMed 36990609Zhu Y, Wen J, Li Q, Chen B, Zhao L, Liu S, Yang Y, Wang S, Lv Y, Li J, Zhang L, Hu Y, Liu M, Xi M. Toripalimab combined with definitive chemoradiotherapy in locally advanced oesophageal squamous cell carcinoma (EC-CRT-001): a single-arm, phase 2 trial. Lancet Oncol. 2023 Apr;24(4):371-382. doi: 10.1016/S1470-2045(23)00060-8.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
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/Cisplatin and Intensity-modulated radiotherapy in people with Unresectable Esophageal Cancer, run by Mian XI 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 10 inclusion and 14 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: finished, as of the sponsor's last update on 23 Aug 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
clinical complete response rate (time frame: 3 months after chemoradiotherapy (plus or minus 14 days)). 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 NCT04005170, 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 23 Aug 2022.