Adjuvant radiotherapy for high-risk esophageal cancer patients

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 testing if adding radiation therapy after surgery can help high-risk patients with esophageal cancer live longer and have better outcomes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 146 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Zhejiang Cancer Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06272214 on ClinicalTrials.gov

What this trial studies

This multicenter, prospective, randomized phase II trial investigates the effectiveness of adjuvant radiotherapy in patients with esophageal squamous cell carcinoma who are at high risk of recurrence after undergoing neoadjuvant chemoradiotherapy and surgery. Eligible participants are those who did not achieve a complete pathological response post-surgery and have specific clinical staging. Patients will be randomly assigned to either an observation group or an adjuvant radiotherapy group, with the latter receiving additional radiotherapy alongside standard postoperative care. The study aims to determine if the addition of radiotherapy improves outcomes for these high-risk patients.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with histologically confirmed esophageal squamous cell carcinoma who have undergone neoadjuvant therapy and surgery without achieving complete pathological response.

Not a fit: Patients who have achieved complete pathological response after surgery or those with unresectable cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option that reduces the risk of cancer recurrence in high-risk esophageal cancer patients.

How similar studies have performed: Other studies have explored the role of adjuvant therapies in esophageal cancer, but the specific combination of adjuvant radiotherapy with immunotherapy in this context is relatively novel.

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.

Where this trial is running

Hangzhou, Zhejiang

• Zhejiang Cancer Hospital — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Youhua Jiang, M.D. — Zhejiang Cancer Hospital
• Study coordinator: Yang Yang, M.d.

Conditions Adjuvant Radiotherapy; Esophageal cancer; Surgery; Neoadjuvant; Chemotherapy; Immunotherapy