Locally Advanced Esophageal Squamous Cell Carcinoma
Conditions
Keywords
esophageal squamous cell carcinoma, neoadjuvant chemoimmunotherapy, radiotherapy
Brief summary
Our previous study, a single-center, prospective, single-arm Phase II study (Keypoint001) has demonstrated the efficacy and safety of neoadjuvant chemotherapy combined with immunotherapy in locally advanced (cT3-4N+M0) esophageal squamous cell carcinoma. The results show that the pathological complete response rate (pCR) reaches 35%, and the major pathological response rate is over 70%, which is much higher than that of patients receiving chemotherapy alone. Meanwhile, no severe adverse drug reactions have been found in terms of safety, so this treatment regimen is safe and reliable. However, the cycle of neoadjuvant immunotherapy is still under exploration. Currently, the mainstream research centers adopt a regimen of 2 to 4 cycles. The exploration results of our center have found that most patients' conditions can be further alleviated after 4 cycles compared with after 2 cycles, but there are still a small number of patients with no obvious remission. Therefore, we consider observing whether patients with no obvious remission can achieve a better pathological response rate through further radiotherapy.
Interventions
DRUGChemotherapy
carboplatin plus nab-paclitaxel
Pembrolizumab
RADIATIONradiotherapy
40-45Gy/20fx，5 times a week
Sponsors
Military 301 Hospital
Peking University Cancer Hospital & Institute
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Peking Union Medical College Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* male or female * Age ≥ 18 years old * Pathological confirmation of esophageal squamous cell carcinoma * Endoscopic ultrasound, enhanced CT scan of the neck, chest, and abdomen, and esophageal magnetic resonance imaging evaluate as T3 or resectable T4 PET/CT、 Cervical, thoracic, and abdominal enhanced CT evaluation of N0 or N+ * No clear distant metastasis (M0) and only cervical or supraclavicular lymph node metastasis (M1a) * Tumor longitudinal diameter ≤ 10cm * The tumor did not involve the dentate line * ECOG score 0 or 1 * No hematological diseases, no liver or kidney dysfunction * Absolute neutrophil count ≥ 1.5 × 109/L * Platelets ≥ 100 × 109/L * Hemoglobin ≥ 11g/L * ALT ≤ 2 times the upper limit of normal value * TBil ≤ 1.5 times the upper limit of normal value * Creatinine clearance rate (Cockroft) ≥ 50ml/min * Obtain informed consent
Exclusion criteria
* T staging evaluation is T1/T2 * PET/CT and other evaluations show distant metastasis (M1) * Planned pregnancy or patients during pregnancy or lactation * History of previous chemotherapy, radiation therapy, or immunotherapy * Previous severe coronary heart disease and heart failure (NYHA grade III/IV) * Previous pulmonary interstitial fibrosis or severe pulmonary dysfunction that cannot tolerate surgery * Previous autoimmune disease requiring systemic treatment within 2 years * Previous immunodeficiency diseases or the need for systemic steroid replacement therapy * Previous motor or sensory neurotoxic diseases * Previous mental illness * Potential diseases that may affect patients' ability to receive planned treatment, such as drug allergies * Acute infectious diseases requiring systemic treatment * Previous HIV, HBV, or HCV infections * Previously received stem cell or solid organ transplantation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological response | After surgery | Postoperative pathology according to CAP classification. |
| 2-year and 5-year overall survival | 2 years and 5 years after therapy | overall survival after 2 years and 5 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse effect incidence | 1 years after therapy | Adverse effect according to CTCAE and RTOG criteria |
| R0 resection rate | After surgery | — |
| postoperative complications | After surgery | postoperative complications according to Clavien-Dindo classification |
| 2-year and 5-year disease-free survival | 2 years and 5 years after therapy | disease-free survival after 2 years and 5 years |
Countries
China
Contacts
Primary ContactLi Li
Outcome results
None listed