Clinical trial NCT06907602: Optimizing Neoadjuvant Treatment Regimens for Locally Advanced Esophageal Squamous Cell Carcinoma
Official title: Optimizing Neoadjuvant Treatment Regimens for Locally Advanced Esophageal Squamous Cell Carcinoma: A Phase II Clinical Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Locally Advanced Esophageal Squamous Cell Carcinoma
Keywords: esophageal squamous cell carcinoma
neoadjuvant chemoimmunotherapy
radiotherapy
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Military 301 Hospital
name: Peking University Cancer Hospital & Institute
name: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
First posted: 2025-04-02
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Pathological response
timeFrame: After surgery
measure: 2-year and 5-year overall survival
timeFrame: 2 years and 5 years after therapy
Secondary outcomes:
measure: Adverse effect incidence
timeFrame: 1 years after therapy
measure: R0 resection rate
timeFrame: After surgery
measure: postoperative complications
timeFrame: After surgery
measure: 2-year and 5-year disease-free survival
timeFrame: 2 years and 5 years after therapy
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
References: