A Prospective, Open-label, Randomized, Controlled Phase II Clinical Trial Exploring the Efficacy and Safety of Thymosin Alpha 1 Combined With PD-1 Monoclonal Antibody and Neoadjuvant Chemoradiotherapy for cStage III Gastroesophageal Junction Adenocarcinoma
Overview
- Phase
- Phase 2
- Intervention
- Immunomodulation
- Conditions
- Not specified
- Sponsor
- The First Affiliated Hospital with Nanjing Medical University
- Enrollment
- 48
- Locations
- 2
- Primary Endpoint
- Complete pathological response (pCR) rate
- Status
- Recruiting
- Last Updated
- 2 months ago
Overview
Brief Summary
This is a prospective, single-center, randomized controlled, phase II clinical trial. The study aims to enroll 48 patients with resectable, locally advanced gastroesophageal junction adenocarcinoma who have not received any treatment. After obtaining informed consent and meeting the inclusion/exclusion criteria, patients were randomly assigned preoperatively in a 1:2 ratio:
Immunomodulation group (n=32): 3 cycles of slulimab combined with SOX combined with radiotherapy and 9 weeks of neoadjuvant thymosin;
Radiochemoimmunotherapy group (n=16): 3 cycles of slulimab combined with SOX combined with radiotherapy;
Radiotherapy was initiated 2-5 days after the start of the second cycle of immunochemotherapy. A 5-10 mm extravasation was made from the endoscopically marked tumor boundary and adjacent metastatic lymph nodes to form a central tumor volume (CTV), and a 5-10 mm extravasation was made to form a partial tumor volume (PTV). The planned PTV treatment time was 44 Gy/22 fractions per minute (F), 5 fractions per week (F/W).
After neoadjuvant therapy, the efficacy of the therapy and the feasibility of radical D2 resection are assessed through imaging examinations. Efficacy evaluation is performed within 2 weeks of the completion of neoadjuvant therapy, and radical gastrectomy is performed within 4-6 weeks. Postoperative treatment is determined jointly by the clinician and the patient based on actual clinical practice.
The primary endpoint is complete pathological response (pCR) rate, defined as the proportion of subjects who have no residual surviving tumor cells under microscopic examination and are negative for lymph nodes.
Safety assessment: Safety assessments are performed after each cycle of neoadjuvant therapy and 30 days postoperatively.
Event follow-up: Follow-up events are then conducted every 3 months for the first year postoperatively, and every 6 months for 1-2 years, up to 2 years postoperatively.
Investigators
Hao Xu
Professor
The First Affiliated Hospital with Nanjing Medical University
Eligibility Criteria
Inclusion Criteria
- •Voluntary written informed consent provided.
- •Age ≥ 18 years and ≤ 80 years at enrollment.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-
- •Life expectancy ≥ 6 months.
- •Diagnosis of gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma by gastroscopy and histopathology. According to AJCC 8th edition staging, abdominal CT assessment confirms clinical stage cStage III (cT3-4aN1-3M0). For GEJ cancers, only Siewert type III and those Siewert type II cases not requiring combined thoracotomy are eligible.
- •Meets the diagnostic criteria for cachexia (based on Fearon's criteria): Either of the following criteria \*\*combined with anorexia or evidence of systemic inflammation\*\*:
- •Unintentional weight loss \>5% within the past 6 months; OR
- •BMI \<18.5 kg/m² and unintentional weight loss \>2% within the past 6 months; OR
- •Appendicular skeletal muscle index meeting criteria for sarcopenia (male \<7.26 kg/m²; female \<5.45 kg/m²) and unintentional weight loss \>2% within the past 6 months.
- •Prior to enrollment, a multidisciplinary assessment involving at least one gastrointestinal surgery attending physician and one radiologist confirms cStage III disease, eligibility for R0 resection with curative intent, patient's agreement to undergo radical surgery, and absence of surgical contraindications as judged by the surgeon.
Exclusion Criteria
- •Subjects who meet any of the following criteria will be excluded from this study:
- •History of other malignancies within the past 5 years or concurrent malignancy. Exceptions include cured localized tumors such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the prostate, cervical carcinoma in situ, breast carcinoma in situ, Stage I lung cancer, Stage I colorectal cancer, etc.
- •Planned or prior organ or bone marrow transplantation.
- •Blood transfusion within 2 weeks prior to the first dose, history of bleeding, or any grade 3 or higher bleeding event (per CTCAE v5.0) within 4 weeks prior to screening.
- •Coagulation disorders or bleeding tendency (INR \>1.5 times the upper limit of normal \[ULN\] without anticoagulant use). Patients receiving therapeutic anticoagulation with agents such as warfarin, heparin, or analogues. Prophylactic use of low-dose warfarin (1 mg orally, once daily) or low-dose aspirin (≤100 mg daily) is permitted if INR ≤1.
- •Arterial or venous thromboembolic events within 6 months prior to screening, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis (except catheter-related thrombosis secondary to prior chemotherapy deemed resolved by the investigator), and pulmonary embolism.
- •Myocardial infarction within 6 months prior to the first dose, or poorly controlled arrhythmias (including QTc interval ≥450 ms for males or ≥470 ms for females, calculated using Fridericia's formula).
- •Cardiac insufficiency meeting NYHA Class III-IV criteria, or left ventricular ejection fraction (LVEF) \<50% as measured by echocardiogram.
- •Urinalysis showing protein ≥++ and confirmed 24-hour urine protein quantification \>1.0 g.
- •Clinically symptomatic pleural effusion or ascites requiring intervention.
Arms & Interventions
Immunomodulation group
Immunomodulation group (n=32): 3 cycles of slulimab combined with SOX combined with radiotherapy and 9 weeks of thymosin-based neoadjuvant therapy;
Intervention: Immunomodulation
Radiochemoimmunotherapy group
Radiochemoimmunotherapy group (n=16): 3 cycles of slulimab combined with SOX combined with radiotherapy.
Intervention: Radiochemoimmunotherapy
Outcomes
Primary Outcomes
Complete pathological response (pCR) rate
Time Frame: from surgery to 1 month after surgery
Defined as the proportion of subjects who have no residual surviving tumor cells under microscopic examination and are negative for lymph nodes
Secondary Outcomes
- Major Pathological Response (MPR)(from preoperative to 10 days postoperative)
- Tumor Regression Grade (TRG)(from preoperative to 10 days postoperative)
- Objective Response Rate (ORR)(before surgery)
- Disease-free Survival (DFS)(2 years after surgery)
- R0 resection rate(from preoperative to 10 days postoperative)
- treatment-related adverse event (TRAE)(from the start of neoadjuvant therapy to 30 days after surgery)
- Complete pathological response (pCR) rate(from surgery to 1 month after surgery)