Trial Title:
Adjuvant Radiotherapy for Esophageal Squamous Cell Carcinoma in the Era of Immunotherapy
NCT ID:
NCT06272214
Condition:
Adjuvant Radiotherapy
Conditions: Official terms:
Carcinoma, Squamous Cell
Esophageal Squamous Cell Carcinoma
Conditions: Keywords:
Esophageal cancer
Surgery
Neoadjuvant
Chemotherapy
Immunotherapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
Adjuvant radiotherapy
Description:
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.
Arm group label:
Adjuvant radiotherapy
Intervention type:
Other
Intervention name:
Observation
Description:
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.
Arm group label:
Observation
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. 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. 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.
2. Subjects in this study are male or female aged ≥18 and ≤75 years at the time of
signing the informed consent form.
3. 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.
4. Histologically confirmed esophageal squamous cell carcinoma.
5. 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).
6. 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%.
7. 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.
8. 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.
9. Subjects are willing and able to comply with scheduled visits, treatment plans,
laboratory tests, and other study requirements.
Exclusion Criteria:
1. Stage IV metastatic esophageal cancer patients with initial diagnosis of metastasis
to visceral organs (such as liver, bone, lung, brain, adrenal gland, etc.).
2. Patients who did not achieve R0 resection after surgery, including R1 and R2
resection.
3. Patients who achieved complete pathological response (pCR) after surgery.
4. Patients with a history of chest radiation therapy.
5. Patients with esophagomediastinal fistula and/or esophagotracheal fistula before
treatment.
6. Pregnant or lactating female patients.
7. Patients who cannot provide informed consent due to psychological, family, social,
or other reasons.
8. 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.
9. Patients who cannot tolerate chemotherapy or radiation therapy due to severe heart,
lung, liver, kidney dysfunction, cachexia, etc.
10. 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.
11. 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).
12. Patients with a history of immunodeficiency diseases; HIV antibody-positive
individuals; those currently using systemic corticosteroids or other
immunosuppressive agents for an extended period.
13. 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).
14. Known active tuberculosis (TB) or suspected active TB subjects, who should undergo
clinical examination for exclusion; known active syphilis infection.
15. 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.
16. A history of interstitial lung disease or non-infectious pneumonitis.
17. 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).
18. Known psychiatric illness, substance abuse, alcoholism, or drug abuse history.
19. 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.
20. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Zhejiang Cancer Hospital
Address:
City:
Hangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
YANG YANG, M.D.
Phone:
+8657188128182
Email:
yangyang@zjcc.org.cn
Investigator:
Last name:
Youhua Jiang
Email:
Principal Investigator
Investigator:
Last name:
Yongling Ji
Email:
Principal Investigator
Start date:
March 1, 2024
Completion date:
March 1, 2029
Lead sponsor:
Agency:
Zhejiang Cancer Hospital
Agency class:
Other
Source:
Zhejiang Cancer Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06272214
