Esophageal Carcinoma, Neoadjuvant Therapy
Conditions
Brief summary
This study is a multicenter, single-arm phase II trial, aiming to evaluate the efficacy and safety of neoadjuvant chemotherapy and immunotherapy combined with concurrent low-dose radiotherapy ± chemoradiotherapy as an adaptive neoadjuvant treatment for previously untreated resectable esophageal squamous cell carcinoma. Compared with neoadjuvant concurrent chemoradiotherapy, the pathological complete response (pCR) rate of neoadjuvant chemoradiotherapy is lower, and non-pCR has a relatively poorer prognosis than pCR. Therefore, how to further increase the pCR rate of neoadjuvant chemoradiotherapy under the premise of minimum toxicity is an important link to improve the efficacy of this treatment strategy. Low-dose radiotherapy provides an option for this strategy. Compared with traditional high-dose radiotherapy, low-dose radiotherapy is very safe, and the extremely low radiotherapy dose causes almost negligible damage to normal tissues. However, it can effectively reshape the immune microenvironment, converting cold tumors into hot tumors. On this basis, combined with immune checkpoint inhibitors, it can achieve effective immune responses in advanced tumors, bringing new hope for the treatment of advanced tumor patients. Low-dose radiotherapy can regulate the tumor immune microenvironment through multiple mechanisms and enhance the body's anti-tumor immune response, thus potentially further improving the efficacy of neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma.
Interventions
Non-cCR group will continue with neoadjuvant concurrent chemoradiotherapy (2Gy\*20f) followed by radical surgery
Sponsors
Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a multicenter, single-arm, phase II study. The purpose of this study is to evaluate the efficacy and safety of adaptive neoadjuvant therapy combining neoadjuvant chemotherapy and immunotherapy with concurrent low-dose radiotherapy ± chemoradiotherapy in treatment-naive patients with resectable esophageal squamous cell carcinoma (ESCC) at stages T1-4aN1-3M0 or T3-4aN0M0.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Inclusion criteria for esophageal cancer: 1. Histologically or cytologically confirmed thoracic esophageal squamous cell carcinoma (ESCC) at stages T1-4aN1-3M0 or T3-4aN0M0 (AJCC 9th edition); Neck color Doppler ultrasound shows no suspicious metastatic lymph nodes. Note: For the determination of T staging, CT combined with MRI or endoscopic ultrasound is used. Research centers are encouraged to use endoscopic ultrasound; Research centers are encouraged to obtain tissue confirmation of lymph node involvement, provided that it can be safely obtained through puncture, EBUS (endobronchial ultrasound), EUS (endoscopic ultrasound) or mediastinoscopy. However, when the boundaries of the lymph nodes are clear and the shortest axis diameter of at least one lymph node is ≥ 2.0 cm, lymph node involvement can be determined by imaging examination (MRI/CT scan); M1 is excluded in FDG-PET/CT or diagnostic-quality CT or MRI scans of the chest, abdomen, pelvis and brain. 2. The lesion is a potentially resectable thoracic esophageal lesion. 3. R0 resection is expected to be achieved. 4. No previous treatment for esophageal tumors has been received. General inclusion requirements: 1. Sign the informed consent form. 2. Male or female aged ≥ 18 years and ≤ 75 years. 3. ECOG performance status is 0 or 1. 4. There are no surgical contraindications based on the evaluation of various organ function tests before surgery. 5. Body weight is greater than 35 kg; The weight loss in the past three months does not exceed 10%. 6. The expected survival time is more than 12 months. 7. Agree to provide previously stored tumor tissue specimens or undergo a biopsy to collect tumor lesion tissue for biomarker analysis. 8. According to the RECIST 1.1 criteria, there is at least one measurable lesion. 9. Good organ function: A.Hematology: White blood cell count ≥ 4×10⁹/L Neutrophil count ≥ 2×10⁹/L Hemoglobin ≥ 9 g/dL Platelet count ≥ 100×10⁹/L B.Liver function: Bilirubin ≤ 1.5 times the upper limit of normal (ULN). Patients with known Gilbert's disease and a serum bilirubin level ≤ 3 times ULN may be eligible for enrollment. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN. In case of liver metastasis, AST/ALT ≤ 5 times ULN. Alkaline phosphatase (ALP) ≤ 3 times ULN. In case of liver or bone metastasis, ALP ≤ 5 times ULN. Albumin ≥ 3 g/dL International Normalized Ratio (INR), Prothrombin Time (PT) or Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 times ULN C.Renal function: Serum creatinine ≤ 1.5 times ULN or creatinine clearance rate ≥ 60 mL/min calculated by the Cockcroft - Gault formula
Exclusion criteria
Cancer - specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pCR | Immediately after the surgery | Pathological complete response rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| EFS | 2 year | EFS is defined as the time from randomization to the occurrence of disease progression or the time of death due to any cause (whichever occurs first), and it is determined by the Independent Review Committee (BIRC) according to the criteria. |
| ORR | Before surgery | — |
| OS | 2 year | — |
| R0 | Immediately after the surgery | — |
Countries
China
Outcome results
None listed