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Adjuvant RadiotherapyPhase 2NCT06272214

Adjuvant Radiotherapy for Esophageal Squamous Cell Carcinoma in the Era of Immunotherapy

A Phase 2 study testing Adjuvant radiotherapy and Observation in people with Adjuvant Radiotherapy, run by Zhejiang Cancer 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

This study is a multicenter, prospective, randomized phase II trial aimed at exploring the value of adjuvant radiotherapy in patients at high risk of recurrence after neoadjuvant chemoradiotherapy for esophageal cancer. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Adjuvant Radiotherapy
What is being tested?
Adjuvant radiotherapy and Observation
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
146 participants
Where
1 siteChina
Study dates
1 Mar 2024to 1 Mar 2029
Phase
Phase 2
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

  • Able to understand and voluntarily sign the written informed consent form, which must be signed before the specified research procedures required by the study are performed.
  • Subjects in this study are male or female aged ≥18 and ≤75 years at the time of signing the informed consent form.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 or Karnofsky Performance Status (KPS) score ≥80 points (see Table 1) at the time of signing the informed consent form.
  • Histologically confirmed esophageal squamous cell carcinoma.
  • The initial patient is a resectable or potentially resectable cT3-4N0 or T1-4N+ patient (AJCC 8th edition) who underwent 2 cycles of neoadjuvant immunotherapy and chemotherapy followed by surgical R0 resection, with postoperative pathology not achieving complete response (non-pCR).
  • Good organ function as determined by the following requirements: a. Hematology (without blood component or growth factor support within 7 days prior to the start of study treatment): i. Absolute neutrophil count (ANC) ≥1.5×109/L (1500/mm3). ii. Platelet count ≥100×109/L (100,000/mm3). iii. Hemoglobin ≥90g/L. b. Renal: i. Calculated creatinine clearance rate (CrCl) ≥50 mL/min. * CrCl will be calculated using the Cockcroft-Gault formula: CrCL (mL/min) = {(140 - age) × weight (kg) × F} / (SCr (mg/dL) × 72) where F = 1 for males and F = 0.85 for females; SCr = serum creatinine. ii. Urinary protein < 2+ or 24-hour urinary protein quantitation < 1.0 g. c. Hepatic: i. Total bilirubin (TBiL) ≤1.5×ULN. ii. AST and ALT ≤2.5×ULN; for subjects with liver metastasis, AST and ALT can be ≤5×ULN. iii. Serum albumin (ALB) ≥28 g/L. d. Coagulation function: International Normalized Ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5×ULN (unless the subject is receiving anticoagulant therapy, and INR and APTT are within the expected range for anticoagulant therapy). e. Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50%.
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  • Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 3 days before the first dose (if urine pregnancy test results cannot be confirmed as negative, a serum pregnancy test must be performed, and serum pregnancy test results will be used) and agree to use highly effective contraception continuously for 120 days after the last dose of study drug; the decision to stop contraception after this time point should be discussed with the investigator.
  • Male subjects who are not surgically sterile and who are sexually active with female partners of childbearing potential must use effective contraception continuously from the screening period through 120 days after the last dose; the decision to stop contraception after this time point should be discussed with the investigator.
  • Subjects are willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study requirements.

Who cannot join

  • Stage IV metastatic esophageal cancer patients with initial diagnosis of metastasis to visceral organs (such as liver, bone, lung, brain, adrenal gland, etc.).
  • Patients who did not achieve R0 resection after surgery, including R1 and R2 resection.
  • Patients who achieved complete pathological response (pCR) after surgery.
  • Patients with a history of chest radiation therapy.
  • Patients with esophagomediastinal fistula and/or esophagotracheal fistula before treatment.
  • Pregnant or lactating female patients.
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  • Patients who cannot provide informed consent due to psychological, family, social, or other reasons.
  • Patients with a history of malignant tumors other than esophageal cancer before enrollment, unless it is non-melanoma skin cancer, in situ cervical cancer, or cured early-stage prostate cancer.
  • Patients who cannot tolerate chemotherapy or radiation therapy due to severe heart, lung, liver, kidney dysfunction, cachexia, etc.
  • Patients with active autoimmune diseases, a history of autoimmune diseases (including but not limited to colitis, hepatitis, hyperthyroidism, etc.), a history of immunodeficiency (including HIV-positive test results), or other acquired or congenital immunodeficiency diseases, organ transplantation, or allogeneic bone marrow transplantation history.
  • Patients with active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10×4 copies/mL), hepatitis C (positive hepatitis C antibody, with hepatitis C virus RNA (HCV-RNA) level higher than the detection limit).
  • Patients with a history of immunodeficiency diseases; HIV antibody-positive individuals; those currently using systemic corticosteroids or other immunosuppressive agents for an extended period.
  • Severe infections occurring within 4 weeks before the first dose, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; active infections treated with systemic anti-infective therapy within 2 weeks before the first dose (excluding antiviral therapy for hepatitis B or hepatitis C).
  • Known active tuberculosis (TB) or suspected active TB subjects, who should undergo clinical examination for exclusion; known active syphilis infection.
  • Vaccination with live vaccines or attenuated live vaccines within 30 days before the first dose, or planned vaccination with live vaccines or attenuated live vaccines during the study period, with the use of inactivated vaccines allowed.
  • A history of interstitial lung disease or non-infectious pneumonitis.
  • A history of myocarditis, cardiomyopathy, malignant arrhythmias. Patients with unstable angina, myocardial infarction, congestive heart failure (New York Heart Association Functional Classification ≥2) or vascular diseases (such as aortic aneurysms at risk of rupture) within 12 months before the first dose or other cardiac injuries that may affect the safety assessment of the study drug (such as poorly controlled arrhythmias, myocardial ischemia).
  • Known psychiatric illness, substance abuse, alcoholism, or drug abuse history.
  • Local or systemic diseases not caused by malignant tumors; or diseases or symptoms secondary to tumors, which may lead to a higher medical risk and/or uncertainty in survival assessment, such as tumor lysis reaction (white blood cell count > 20×109/L), cachexia presentation (weight loss > 10% in the 3 months before screening), etc.
  • Any condition considered by the investigator as posing a risk to the subject, interfering with the evaluation of the study drug, or affecting the interpretation of study results.

Trial locations and contacts

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

YANG YANG, M.D. contact

+8657188128182

yangyang@zjcc.org.cn

Weizhen Xu contact

xuwz@zjcc.org.cn

China1 site, 1 recruiting

  • Zhejiang Cancer Hospital

    Hangzhou, Zhejiang

    YANG YANG, M.D., +8657188128182, yangyang@zjcc.org.cn

    Youhua Jiang

    Recruiting

Other trials in China

About this study

Official title: The Role of Adjuvant Radiotherapy in the Treatment for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma After Neoadjuvant Chemotherapy Combined With Immunotherapy: A Multi-center, Phase II Randomized Clinical Study

This study is a multicenter, prospective, randomized phase II trial aimed at exploring the value of adjuvant radiotherapy in patients at high risk of recurrence after neoadjuvant chemoradiotherapy for esophageal cancer. The study primarily includes patients with esophageal cancer who underwent neoadjuvant chemoradiotherapy and surgery and did not achieve complete pathological response (non-pCR) postoperatively and were defined as preoperative clinical stage at T3-4N+M0.

Eligible patients will be randomized in a 1:1 ratio into two groups: the observation group and the adjuvant radiotherapy group. The control group consists of patients who receive surgery after neoadjuvant chemotherapy combined with immunotherapy for esophageal cancer, followed by maintenance therapy with PD1/PDL1 inhibitors for up to 1 year or until tumor progression. The adjuvant radiotherapy group receives additional adjuvant radiotherapy on top of the control group's treatment. The specific treatment process involves receiving 2 cycles of neoadjuvant chemotherapy combined with immunotherapy (PD1/PDL1 inhibitors) before potentially curative esophageal cancer surgery. The chemotherapy regimen includes paclitaxel in combination with platinum agents, with a preference for albumin-bound paclitaxel (280mg/m2 on Day 1, or 100mg on Days 1, 8, and 15) in combination with carboplatin (AUC=5). Following surgery, patients start adjuvant radiotherapy 4-6 weeks after the operation, with a radiation dose of 45Gy/25F/5W, completed no later than 8 weeks post-surgery. Two weeks after completing radiotherapy, patients continue with immunotherapy maintenance therapy for up to 1 year or until tumor progression. Subsequently, follow-up visits are scheduled every 3-4 months for the first 3 years, every 6 months for the next 2 years, and annually thereafter. The primary endpoint is 2-year disease-free survival (DFS), and secondary endpoints include overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), recurrence patterns, and safety assessment. Additionally, the study will explore biomarkers predicting treatment efficacy and adverse reactions in subjects, including PD-L1 expression, ctDNA clearance status, infiltrating immune cell types and quantities, cytokine expression, and other tumor biomarkers. This exploration aims to guide stratified precision treatment for patients.

Being tested
Adjuvant radiotherapy, Observation
Keywords
Esophageal cancer, Surgery, Neoadjuvant, Chemotherapy, Immunotherapy
Medical subject headings
Esophageal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Adjuvant radiotherapyRadiation

    The start time for radiotherapy is 4-6 weeks after surgery, typically not exceeding 8 weeks. Intensity-modulated radiation therapy (IMRT) will be used, with a total dose of 45Gy administered in 25 fractions, five times per week.

    The recommended target delineation for radiotherapy is based on the Chinese guidelines for radiation therapy of esophageal cancer, which mainly covers the high-risk lymph node area.

  • ObservationOther

    Patients receive surgery after neoadjuvant chemotherapy combined with immunotherapy for esophageal cancer, followed by active survillance and maintenance therapy with PD1/PDL1 inhibitors for up to 1 year or until tumor progression.

Study groups in NCT06272214
Study groupRoleWhat they receive
Adjuvant radiotherapyExperimentalFollowing surgery, patients start adjuvant radiotherapy 4-6 weeks after the operation, with a radiation dose of 45Gy/25F/5W, completed no later than 8 weeks post-surgery. Two weeks after completing radiotherapy, patients continue with immunotherapy maintenance therapy for up to 1 year (17 cycles Q3W) or until tumor progression.
Receives: Radiation: Adjuvant radiotherapy
ObservationActive comparatorPatients receive surgery after neoadjuvant chemotherapy combined with immunotherapy for esophageal cancer, followed by active survillance and maintenance therapy with PD1/PDL1 inhibitors for up to 1 year (17 cycles Q3W) or until tumor progression.
Receives: Other: Observation

What is being measured

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

  1. 2-year DFS

    Time between enrollment and recurrence of disease or death

    Measured: 24 months

Secondary outcomes (6)

  1. OS

    Overall survival，Time between enrollment and death

    Measured: occurence or end of follow-up（2 years after enrollment）, which comes first

  2. LRFS

    Time between enrollment and local recurrence

    Measured: 24 months

  3. DMFS

    distant metastasis free survival,Time between enrollment and distant metastasis

    Measured: 24 months

  4. HRQoL

    The EORTC QLQ-C30 questionnaire will be used. Scale scores will be calculated following the scoring guidelines of the EORTC questionnaires. Scores will be summarized by means of the appropriate descriptive statistics (mean + SD or median + IQR) at each measurement point.

    Measured: 3 months, 1year, 2 years after surgery

  5. Adverse effects recorded during radiotherapy and PD1/PDL1 inhibitors maintaince period

    safety

    Measured: occurence or end of follow-up（2 years after enrollment), which comes first

  6. Incidence of Recurrence

    including local recurrence and distant metastasis

    Measured: occurence or end of follow-up（2 years after enrollment), which comes first

Timeline

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

  1. First posted22 Feb 2024
  2. Study start1 Mar 2024
  3. Primary completion1 Mar 2027 (estimated)
  4. Study completion1 Mar 2029 (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
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
146 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06272214
Sponsor's protocol ID
IIT-2024-048
Status last verified
Jul 2024
First submitted
4 Feb 2024
Last updated
16 Jul 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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

  • Kelly RJ, Ajani JA, Kuzdzal J, Zander T, Van Cutsem E, Piessen G, Mendez G, Feliciano J, Motoyama S, Lievre A, Uronis H, Elimova E, Grootscholten C, Geboes K, Zafar S, Snow S, Ko AH, Feeney K, Schenker M, Kocon P, Zhang J, Zhu L, Lei M, Singh P, Kondo K, Cleary JM, Moehler M; CheckMate 577 Investigators. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med. 2021 Apr 1;384(13):1191-1203. doi: 10.1056/NEJMoa2032125.

    PubMed 33789008

  • Luo H, Lu J, Bai Y, Mao T, Wang J, Fan Q, Zhang Y, Zhao K, Chen Z, Gao S, Li J, Fu Z, Gu K, Liu Z, Wu L, Zhang X, Feng J, Niu Z, Ba Y, Zhang H, Liu Y, Zhang L, Min X, Huang J, Cheng Y, Wang D, Shen Y, Yang Q, Zou J, Xu RH; ESCORT-1st Investigators. Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial. JAMA. 2021 Sep 14;326(10):916-925. doi: 10.1001/jama.2021.12836.

    PubMed 34519801

  • van den Ende T, de Clercq NC, van Berge Henegouwen MI, Gisbertz SS, Geijsen ED, Verhoeven RHA, Meijer SL, Schokker S, Dings MPG, Bergman JJGHM, Haj Mohammad N, Ruurda JP, van Hillegersberg R, Mook S, Nieuwdorp M, de Gruijl TD, Soeratram TTD, Ylstra B, van Grieken NCT, Bijlsma MF, Hulshof MCCM, van Laarhoven HWM. Neoadjuvant Chemoradiotherapy Combined with Atezolizumab for Resectable Esophageal Adenocarcinoma: A Single-arm Phase II Feasibility Trial (PERFECT). Clin Cancer Res. 2021 Jun 15;27(12):3351-3359. doi: 10.1158/1078-0432.CCR-20-4443. Epub 2021 Jan 27.

    PubMed 33504550

  • Yin J, Yuan J, Li Y, Fang Y, Wang R, Jiao H, Tang H, Zhang S, Lin S, Su F, Gu J, Jiang T, Lin D, Huang Z, Du C, Wu K, Tan L, Zhou Q. Neoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial. Nat Med. 2023 Aug;29(8):2068-2078. doi: 10.1038/s41591-023-02469-3. Epub 2023 Jul 24.

    PubMed 37488287

  • Matsuda S, Kawakubo H, Okamura A, Takahashi K, Toihata T, Takemura R, Mayanagi S, Hirata K, Irino T, Hamamoto Y, Takeuchi H, Facs, Watanabe M, Kitagawa Y. Distribution of Residual Disease and Recurrence Patterns in Pathological Responders After Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma. Ann Surg. 2022 Aug 1;276(2):298-304. doi: 10.1097/SLA.0000000000004436. Epub 2020 Oct 16.

    PubMed 33074909

  • Yang Y, Liu J, Liu Z, Zhu L, Chen H, Yu B, Zhang R, Shao J, Zhang M, Li C, Li Z. Two-year outcomes of clinical N2-3 esophageal squamous cell carcinoma after neoadjuvant chemotherapy and immunotherapy from the phase 2 NICE study. J Thorac Cardiovasc Surg. 2024 Mar;167(3):838-847.e1. doi: 10.1016/j.jtcvs.2023.08.056. Epub 2023 Sep 9.

    PubMed 37696429

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Adjuvant radiotherapy and Observation in people with Adjuvant Radiotherapy, run by Zhejiang Cancer 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 20 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 16 Jul 2024. 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?

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?

Contact YANG YANG, M.D. (+8657188128182, yangyang@zjcc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

2-year DFS (time frame: 24 months). 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 NCT06272214, which also lists 7 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 16 Jul 2024.

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