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Esophageal Squamous Cell Carcinoma Stage IIPhase 2/3iCROSSNCT04973306

Neoadjuvant Immunotherapy Plus CRT Versus Neoadjuvant CRT for Locally Advanced Resectable ESCC

A Phase 2/3 study testing Neoadjuvant Chemoradiotherapy, Tislelizumab and Ivor-Lewis or Mckeown Esophagectomy(Mckeown Esophagectomy recommended) in people with Esophageal Squamous Cell Carcinoma Stage II and Esophageal Squamous Cell Carcinoma Stage III, run by Shanghai Zhongshan Hospital at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The purpose of this study was to evaluate the safety, feasibility and outcome of anti-PD-1 antibody (Tislelizumab, BeiGene) combined with neoadjuvant chemoradiotherapy versus neoadjuvant chemoradiotherapy followed by minimally invasive esophagectomy for locally advanced resectable esophageal squamous cell carcinoma… Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Neoadjuvant Chemoradiotherapy, Tislelizumab and Ivor-Lewis or Mckeown Esophagectomy(Mckeown Esophagectomy recommended)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
176 participants
Where
1 siteChina
Study dates
2 Mar 2022to Jul 2027
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

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

  • Histologically-confirmed esophageal squamous cell carcinoma and whose tissue samples were taken before treatment;
  • Tumors of the esophagus are located in the thoracic cavity;
  • Pre-treatment stage as clinical II-III (AJCC/UICC 8th Edition)
  • Age is between 18 years and 75 years;
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and expected survival time ≥12 months;
  • Adequate cardiac function. All patients should perform ECG, and those with a cardiac history or ECG abnormality should perform echocardiography with the left ventricular ejection fraction > 50 %;
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  • Adequate respiratory function with FEV1≥1.2L, FEV1%≥50% and DLCO≥50% shown in pulmonary function tests ;
  • Adequate bone marrow function (White Blood Cells >4x10^9 /L; Neutrophil >2.0×10^9 /L; Hemoglobin > 90 g/L; platelets>100x10^9 /L);
  • Adequate liver function (Total bilirubin <1.5x Upper Level of Normal (ULN); Aspartate transaminase(AST) and Alanine transaminase (ALT) <1.5x ULN);
  • Adequate renal function (Glomerular filtration rate (CCr) >60 ml/min; serum creatinine (SCr) ≤120 µmol/L);
  • The patient has provided written informed consent and is able to understand and comply with the study;

Who cannot join

  • Patients with histological non-squamous cell carcinoma;
  • Patients with advanced non-operable or metastatic esophageal cancer;
  • Pre-treatment stage as cM+, cN3 or cT4b(non-curatively-resectable verified by the local surgical investigator, AJCC/UICC 8th Edition) or cTis-1a, cT1bN0;
  • Patients with another previous or current malignant disease which is likely to interfere with treatment or the assessment of response in the judgement of the local surgical investigator;
  • Patients who have received or are receiving other chemotherapy, radiotherapy or targeted therapy;
  • Other Exclusion Criteria:
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  • Patients with autoimmune diseases history;
  • Recently or currently taking Glucocorticoids or Immunosuppressants;
  • Patients who underwent immunotherapy in the past;
  • Allergy to any antibody drugs or allergy to Paclitaxel and Carboplatin.
  • Past or currently suffering from chronic or recurrent autoimmune diseases;
  • Patients with active infection of immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); HIV seropositivity; HBV DNA or HCV RNA positive;
  • Patients with organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation);
  • Patients with severe systematic intercurrent disease, such as active infection or poorly controlled diabetes; coagulation disorders; hemorrhagic tendency or under treatment of thrombolysis or anticoagulant therapy;
  • Any patient with a significant medical condition which is thought unlikely to tolerate the therapies. Such as cardiac disease (e.g. symptomatic coronary artery disease or myocardial infarction within last 12 months), clinically-significant lung disease, clinically-significant bone marrow, liver, renal function disorder;
  • Pregnant or lactating women and fertile women who will not be using contraception during the trial;
  • Participation in another intervention clinical trial with interference to the chemotherapeutic or chemoradiotherapeutic intervention during this study or during the last 30 days prior to informed consent;
  • Expected lack of compliance with the protocol.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

China1 site, 1 recruiting

  • Shanghai Zhongshan Hospital

    Shanghai, 200032

    Lijie Tan, MD, +8621-64041990-692017, tan.lijie@zs-hospital.sh.cn

    Recruiting

Other trials in China

About this study

Official title: Neoadjuvant Immunotherapy Combined With Chemoradiotherapy Versus Neoadjuvant Chemoradiotherapy for Locally Advanced Resectable Esophageal Squamous Cell Carcinoma (cII-III Stage): A Multi-center Prospective Randomized Clinical Trial

The purpose of this study was to evaluate the safety, feasibility and outcome of anti-PD-1 antibody (Tislelizumab, BeiGene) combined with neoadjuvant chemoradiotherapy versus neoadjuvant chemoradiotherapy followed by minimally invasive esophagectomy for locally advanced resectable esophageal squamous cell carcinoma (cII-III Stage) patient.

Read the detailed description

It is a prospective randomized phase II\&III clinical trial sponsored by Shanghai Zhongshan Hospital with other twelve hospitals in China participating in. 476 patients with locally advanced resectable esophageal squamous cell carcinoma (cII-III Stage) are recruited and randomly assigned into the neoadjuvant chemoradiotherapy combined with immunotherapy group (nCRT plus anti-PD-1 Group) and the neoadjuvant chemoradiotherapy group (nCRT Group) according to the proportion of 1:1. The safety, efficacy of protocols and prognosis of patients are compared between the two regimens.

Being tested
Neoadjuvant Chemoradiotherapy, Tislelizumab, Ivor-Lewis or Mckeown Esophagectomy(Mckeown Esophagectomy recommended)
Keywords
Esophageal Squamous Cell Carcinoma
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.

  • Neoadjuvant ChemoradiotherapyProcedure or surgery

    Chemotherapy: carboplatin (AUC 2 mg/mL per min) and paclitaxel (50 mg/m2 of body-surface area) were administered intravenously for five cycles, starting on days 1, 8, 15, 22, and 29. For each cycle, Carboplatin and paclitaxel were administered 30 minutes apart.

    Radiotherapy: A total radiation dose of 41.4 Gy was given in 23 fractions of 1.8 Gy, 5 days per week (Radiotherapy was performed on the 2nd, 3rd, 4th, 5th, and 6th day in each cycle, and only 3 times in the 5th cycle)

  • TislelizumabDrug

    Also called anti-PD-1 antibody

    Tislelizumab (200mg/time) was administered intravenously on the 1st and 22nd day.

    The intravenous injection lasts about 30 minutes (micropump is recommended, intravenous bolus is prohibited, duration should be not less than 20 minutes and not more than 60 minutes);

  • Ivor-Lewis or Mckeown Esophagectomy(Mckeown Esophagectomy recommended)Procedure or surgery

    After neoadjuvant therapy, patients in groups receive Ivor-Lewis or Mckeown Esophagectomy (Mckeown Esophagectomy recommended)

Study groups in NCT04973306
Study groupRoleWhat they receive
Neoadjuvant chemoradiotherapy combined with anti-PD-1 antibodyExperimentalNeoadjuvant chemoradiotherapy (NCRT) combined with tislelizumab is performed followed by Ivor-Lewis or Mckeown esophagectomy in enrolled patients.
Receives: Procedure: Neoadjuvant Chemoradiotherapy; Drug: Tislelizumab; Procedure: Ivor-Lewis or Mckeown Esophagectomy(Mckeown Esophagectomy recommended)
Neoadjuvant chemoradiotherapyActive comparatorNeoadjuvant chemoradiotherapy (NCRT) is performed followed by Ivor-Lewis or Mckeown esophagectomy in enrolled patients.
Receives: Procedure: Neoadjuvant Chemoradiotherapy; Procedure: Ivor-Lewis or Mckeown Esophagectomy(Mckeown Esophagectomy recommended)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathological response rate(pCR)

    The resected specimen following neo-adjuvant treatment are assessed by using standardized work up of the resection specimen in the pathology department and standardized histological criteria for tumor regression grading. The degree of histomorphologic regression is clarified into four categories as follows: grade 1, no evidence of vital residual tumor cells (pathological complete response); grade 2, less than 10% vital residual tumor cells; grade 3, 10 to 50%; and grade 4, more than 50%.

    Measured: Up to the date of pathological reports obtained since the date of randomization, up to 12 months

  2. Overall survival(OS)

    Measured: Up to the date of death of any causes since the date of randomization, up to 36 months

Secondary outcomes (8)

  1. Treatment related complications

    Number and severity of adverse events that are related to treatment of each patients (including adverse events associated with neoadjuvant chemoradiotherapy, immunotherapy(irAE) and surgery), and hospital re-admission. Treatment-related adverse events as assessed by CTCAE v5.0

    Measured: Up to 1 month after surgery since the data of randomization, up to 13 months

  2. Progression-free survival(PFS)

    Disease recurrence is defined as locoregional (esophageal bed or anastomotic or regional lymph nodes) or metastatic (supraclavicular lymph nodes or distant organs)

    Measured: Up to the date of disease recurrence since the date of randomization, up to 36 months

  3. R0 resection rate

    No vital tumor is presented at the proximal, distal, or circumferential resection margin, it is considered to be R0 resection. If a vital tumor is shown at 1 mm or less from the proximal, distal, or circumferential resection margin, it is considered to be microscopically positive (R1).

    Measured: Up to the date of pathological reports obtained since the date of randomization, up to 12 months

  4. Number and Location of positive lymph nodes

    According to pathological reports, record the number and location of positive lymph nodes

    Measured: Up to the date of pathological reports obtained since the date of randomization, up to 12 months

  5. Overall Quality of life

    Overall Quality of life is respectively evaluated at randomization and 1 month, 3 month, 6 month and yearly after surgery among patients by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 Scale (EORTC QLQ-C30)

    Measured: Up to the end of follow-up since the data of surgery, up to 36 months

  6. Quality of life in eating and swallowing function

    Quality of life in eating and swallowing function is respectively evaluated at randomization and 1 month, 3 month, 6 month and yearly after surgery among patients by using the EORTC QLQ-OES18 Scale

    Measured: Up to the end of follow-up since the data of surgery, up to 36 months

  7. Recurrence-free survival (RFS)

    RFS is defined in resected patients who achieved an R0 or R1 resection as the time interval from surgery to the date of first recurrence (local, regional or distant) or death, whichever comes first.

    Measured: Up to the date of disease recurrence since the date of surgery, up to 36 months

  8. Correlation between genetic profile and tumor response

    Genetic profile (assessed by whole exome sequencing, T-cell receptor sequencing, RNA sequencing) .illumina HiSeq and Nanostring platforms will be used to evaluate the patient's genetic profile. The tumor response will be evaluated by an experienced thoracic tumor pathologist in our center through Tumor regression grading (TRG) systems.

    Measured: Up to the end of follow-up since the data of surgery, up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jul 2021
  2. Study start2 Mar 2022
  3. Primary completionJul 2024 (estimated)
  4. Study completionJul 2027 (estimated)

Resources

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
176 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04973306
Sponsor's protocol ID
B2021-369R
Acronym
iCROSS
Status last verified
Jun 2022
First submitted
28 Jun 2021
Last updated
30 Jun 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: According to the regulations on the management of human genetic resources of the People's Republic of China, we will not be able to share Individual Participant Data

Publications

  • Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. doi: 10.3322/caac.21338. Epub 2016 Jan 25.

    PubMed 26808342

  • van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074-84. doi: 10.1056/NEJMoa1112088.

    PubMed 22646630

  • Liu S, Wen J, Yang H, Li Q, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Zhao L, Liu H, Hu Y, Liu M, Fu J, Xi M. Recurrence patterns after neoadjuvant chemoradiotherapy compared with surgery alone in oesophageal squamous cell carcinoma: results from the multicenter phase III trial NEOCRTEC5010. Eur J Cancer. 2020 Oct;138:113-121. doi: 10.1016/j.ejca.2020.08.002. Epub 2020 Aug 30.

    PubMed 32877795

  • McDermott DF, Atkins MB. PD-1 as a potential target in cancer therapy. Cancer Med. 2013 Oct;2(5):662-73. doi: 10.1002/cam4.106. Epub 2013 Jul 21.

    PubMed 24403232

  • Doi T, Piha-Paul SA, Jalal SI, Saraf S, Lunceford J, Koshiji M, Bennouna J. Safety and Antitumor Activity of the Anti-Programmed Death-1 Antibody Pembrolizumab in Patients With Advanced Esophageal Carcinoma. J Clin Oncol. 2018 Jan 1;36(1):61-67. doi: 10.1200/JCO.2017.74.9846. Epub 2017 Nov 8.

    PubMed 29116900

  • Yamamoto S, Kato K. Immuno-oncology for esophageal cancer. Future Oncol. 2020 Nov;16(32):2673-2681. doi: 10.2217/fon-2020-0545. Epub 2020 Aug 11.

    PubMed 32777942

  • Huang J, Xu J, Chen Y, Zhuang W, Zhang Y, Chen Z, Chen J, Zhang H, Niu Z, Fan Q, Lin L, Gu K, Liu Y, Ba Y, Miao Z, Jiang X, Zeng M, Chen J, Fu Z, Gan L, Wang J, Zhan X, Liu T, Li Z, Shen L, Shu Y, Zhang T, Yang Q, Zou J; ESCORT Study Group. Camrelizumab versus investigator's choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2020 Jun;21(6):832-842. doi: 10.1016/S1470-2045(20)30110-8. Epub 2020 May 13.

    PubMed 32416073

  • Liao XY, Liu CY, He JF, Wang LS, Zhang T. Combination of checkpoint inhibitors with radiotherapy in esophageal squamous cell carcinoma treatment: A novel strategy. Oncol Lett. 2019 Nov;18(5):5011-5021. doi: 10.3892/ol.2019.10893. Epub 2019 Sep 19.

    PubMed 31612012

  • Li C, Zhao S, Zheng Y, Han Y, Chen X, Cheng Z, Wu Y, Feng X, Qi W, Chen K, Xiang J, Li J, Lerut T, Li H. Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). Eur J Cancer. 2021 Feb;144:232-241. doi: 10.1016/j.ejca.2020.11.039. Epub 2020 Dec 26.

    PubMed 33373868

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Neoadjuvant Chemoradiotherapy, Tislelizumab and Ivor-Lewis or Mckeown Esophagectomy(Mckeown Esophagectomy recommended) in people with Esophageal Squamous Cell Carcinoma Stage II and Esophageal Squamous Cell Carcinoma Stage III, 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 11 inclusion and 18 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: looking for participants now, as of the sponsor's last update on 30 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 combined 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.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological response rate(pCR) (time frame: Up to the date of pathological reports obtained since the date of randomization, up to 12 months). 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?

On the ClinicalTrials.gov record for NCT04973306, which also lists 9 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 30 Jun 2022.

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