A Single Arm, Prospective, Exploratory, Single Center Phase II Clinical Study of Serplulimab Combined With Synchronous Radiochemotherapy for the Treatment of Locally Advanced Esophageal Squamous Cell Cancer in Elderly Patients With Non Surgical Resectable Lesions Research Plan
Overview
- Phase
- Phase 2
- Intervention
- Serplulimab
- Conditions
- Esophageal Carcinoma
- Sponsor
- The First Affiliated Hospital with Nanjing Medical University
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- mPFS
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This study is a Single Arm, Prospective, Exploratory, Single Center Phase II Clinical Study to evaluate the effectiveness of the combination of Serplulimab and Concurrent Chemoradiotherapy in the treatment of elderly patients with locally advanced esophageal cancer who cannot be treated surgically.Subjects can be enrolled into this study only if they meet inclusion criteria and do not meet exclusion criteria.
Detailed Description
It is expected that 50 patients will be enrolled, and patients who meet the enrollment criteria will undergo esophagoscopy, esophageal barium meal examination, chest contrast-enhanced CT, abdominal ultrasound, electrocardiogram, blood routine, whole body bone scan, liver and kidney function and other examinations before treatment, and esophageal ultrasound if necessary. Patients who received esophageal ultrasound were staged by esophageal ultrasound results, and those without esophageal ultrasound were mainly staged according to the cervical chest and epigastric contrast CT and esophageal barium plates, and clinical staging was performed according to the AJCC staging standard. After the combination of Serplulimab and concurrent chemoradiotherapy, adverse reactions and efficacy evaluation were observed. The expected result is that the local control rate of Serplulimab combined with chemoradiotherapy is improved in patients with locally advanced elderly esophageal squamous cell carcinoma, and there is no significant increase in adverse reactions, and serological indicators such as PDL-1 CPS can be used as prognostic indicators for esophageal malignancy and have certain guiding significance for treatment. PD-1 monoclonal antibody can be used in locally advanced elderly esophageal cancer patients who cannot tolerate chemotherapy, with good short-term efficacy and tolerable toxic side effects, which further provides reference value for clinical guidance.
Investigators
Eligibility Criteria
Inclusion Criteria
- •The patient voluntarily participated in this study, signed an informed consent form, had good compliance, and cooperated with follow-up;
- •Age 75 and above, both male and female;
- •Patients with locally advanced esophageal squamous cell carcinoma confirmed by histology and clinically classified as stage II-IVa that cannot be surgically removed (including non resectable, contraindications to surgery, or refusal to undergo surgery) (according to the 8th edition of AJCC staging, the pre-treatment clinical staging is cT1N2-3M0, cT2-4bN0-3M0);
- •PDL1 detection result CPS ≥ 1
- •There are measurable and/or unmeasurable lesions that meet the criteria for evaluating the efficacy of solid tumors (RECIST 1.1);
- •Have not received any systematic anti-tumor treatment in the past (including but not limited to systemic chemotherapy, radiotherapy, molecular targeted drug therapy, immunotherapy, biological therapy, local treatment, and other research treatment drugs);
- •ECOG: 0-1 points (see Attachment 1);
- •It is recommended to provide fresh or archived tumor tissue samples within 6 months (fresh samples are preferred) for biomarker analysis (such as PD-L1). The sample type is a formalin fixed, paraffin embedded \[FFPE\] tumor tissue block or at least 5 unstained, 3-5 thick pieces μ FFPE tumor tissue slice of m;
- •Expected survival time ≥ 3 months;
- •The functions of important organs meet the following requirements (no blood components or cell growth factors are allowed to be used 2 weeks before the start of screening examination): Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Platelets ≥ 100 × 109/L; Hemoglobin ≥ 9g/dL; Serum albumin ≥ 2.8g/dL; Total bilirubin ≤ 1.5 x ULN, ALT, AST, and/or AKP ≤ 2.5 x ULN; Serum creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 60mL/min (calculated according to Cockcroft Gault formula, see Annex 2); International standardized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (for stable dose anticoagulant therapy such as low molecular weight heparin or warfarin, and INR can be screened within the expected therapeutic range of anticoagulants);
Exclusion Criteria
- •History of esophageal cancer surgery;
- •Previous history of fistula caused by primary tumor infiltration;
- •There is a higher risk of gastrointestinal bleeding, esophageal fistula, or esophageal perforation;
- •Subjects with poor nutritional status and a weight loss of ≥ 10% within the first two months of screening showed no significant improvement after management and intervention;
- •Has undergone major surgery or had serious trauma within the first 4 weeks prior to the use of the investigational drug;
- •There are uncontrollable pleural effusion, pericardial effusion, or ascites that require repeated drainage;
- •Have received or are currently receiving any of the following treatments in the past:
- •Anti PD-1 or anti PD-L1 antibody therapy, chemotherapy, radiotherapy, targeted therapy;
- •Received any investigational medication within 4 weeks prior to the first use of the investigational medication;
- •Subjects who require systemic treatment with corticosteroids (\>10 mg prednisone equivalent dose per day) or other immunosuppressants within 2 weeks prior to the first use of the study drug are excluded from the use of corticosteroids for local esophageal inflammation and prevention of allergies, nausea, and vomiting. Other special circumstances require communication with the sponsor. In the absence of active autoimmune diseases, it is allowed to inhale or locally use steroids and adrenal cortex hormone replacement with a dose greater than 10mg/day of prednisone efficacy dose;
Arms & Interventions
Assigned Interventions
Treatment options Serplulimab （4.5mg/Kg every 3 weeks）combined with chemoradiotherapy (Oral chemotherapy with the tigio regimen is given on days 1 to 2 of radiotherapy, with the drug dose 40-60mg BID, and the oral tigio course from Monday to Friday is synchronized with radiation therapy) for the treatment of locally advanced elderly esophageal cancer patients, in which the tigio regimen with good clinical tolerability was selected for chemotherapy to evaluate the short-term efficacy and toxic side effects
Intervention: Serplulimab
Outcomes
Primary Outcomes
mPFS
Time Frame: up to one year
Median Progression-Free-Survival
Secondary Outcomes
- OS(through study completion, an average of 18 month)
- DOR(through study completion, an average of 18 month)
- Toxic side reactions(through study completion, an average of 18 month)
- ORR(through study completion, an average of 18 month)