Combining Serplulimab with Chemoradiotherapy for Elderly Patients with Advanced Esophageal Cancer

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

This study is testing if combining a new drug called Serplulimab with standard chemotherapy and radiation can help older patients with advanced esophageal cancer who can't have surgery feel better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 75 Years and up
• Sex: All
• Sponsor: The First Affiliated Hospital with Nanjing Medical University (Academic / other)
• Drugs / interventions: serplulimab, chemotherapy, immunotherapy, prednisone
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT06354218 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of Serplulimab in combination with concurrent chemoradiotherapy for elderly patients aged 75 and above who have locally advanced esophageal squamous cell carcinoma that cannot be surgically removed. The study will enroll 50 patients who meet specific inclusion criteria and will undergo various examinations before treatment. The primary focus is to assess the local control rate of the treatment while monitoring for adverse reactions and evaluating serological indicators as potential prognostic markers. The trial aims to provide insights into a treatment option for patients who cannot tolerate chemotherapy.

Who should consider this trial

Good fit: Ideal candidates are elderly patients aged 75 and above with locally advanced esophageal squamous cell carcinoma that is not amenable to surgical intervention.

Not a fit: Patients who have previously received systemic anti-tumor treatments or those with esophageal cancer that is resectable may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve local control rates and provide a viable option for elderly patients with advanced esophageal cancer who cannot undergo surgery.

How similar studies have performed: While similar approaches have been explored, this specific combination of Serplulimab with concurrent chemoradiotherapy in elderly patients is relatively novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* 1\. The patient voluntarily participated in this study, signed an informed consent form, had good compliance, and cooperated with follow-up; 2. Age 75 and above, both male and female; 3. 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); 4. PDL1 detection result CPS ≥ 1 5. There are measurable and/or unmeasurable lesions that meet the criteria for evaluating the efficacy of solid tumors (RECIST 1.1); 6. 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); 7. ECOG: 0-1 points (see Attachment 1); 8. 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; 9. Expected survival time ≥ 3 months; 10. 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:

* 1\. History of esophageal cancer surgery; 2. Previous history of fistula caused by primary tumor infiltration; 3. There is a higher risk of gastrointestinal bleeding, esophageal fistula, or esophageal perforation; 4. 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; 5. Has undergone major surgery or had serious trauma within the first 4 weeks prior to the use of the investigational drug; 6. There are uncontrollable pleural effusion, pericardial effusion, or ascites that require repeated drainage; 7. Have received or are currently receiving any of the following treatments in the past:

  1. Anti PD-1 or anti PD-L1 antibody therapy, chemotherapy, radiotherapy, targeted therapy;
  2. Received any investigational medication within 4 weeks prior to the first use of the investigational medication;
  3. 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;
  4. Individuals who have received anti-tumor vaccines or have received live vaccines within 4 weeks prior to the first administration of the investigational drug; 8. Have any history of active autoimmune diseases or autoimmune diseases (such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism); Excluding patients with vitiligo or those who have recovered from asthma/allergies of the same age and do not require any intervention in adulthood; Patients with autoimmune mediated hypothyroidism treated with thyroid replacement hormone at a stable dose and type I diabetes patients treated with insulin at a stable dose can be included; 9. Have a history of immunodeficiency, including HIV testing positive, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation and allogeneic bone marrow transplantation; 10. Subjects with uncontrolled clinical symptoms or diseases of the heart, such as (1) NYHA II and above heart failure, (2) unstable angina, (3) myocardial infarction within 1 year, and (4) clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention; 11. Serious infections (CTC AE\>Level 2) occurred within 4 weeks prior to the first use of the investigational drug, such as severe pneumonia, bacteremia, and infection complications that require hospitalization treatment; Baseline chest imaging examination suggests the presence of active pulmonary inflammation and symptoms and signs of infection within 2 weeks prior to the first use of the study drug, requiring oral or intravenous antibiotic treatment, except for prophylactic antibiotic use; 12. Have a history of interstitial lung disease and non infectious pneumonia, and pulmonary function tests confirm ≥ grade 3 pulmonary insufficiency; 13. Patients who have been diagnosed with active pulmonary tuberculosis infection through medical history or CT examination, or have a history of active pulmonary tuberculosis infection within one year before enrollment, or have a history of active pulmonary tuberculosis infection more than one year before but have not received formal treatment; 14. The subject has active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (hepatitis C antibody positive, and HCV RNA above the detection limit of the analysis method); 15. There are abnormal laboratory test values of sodium, potassium, and calcium greater than level 1 within the first two weeks of enrollment, which cannot be improved after treatment; 16. Known allergic reactions, hypersensitivity reactions, or contraindications to macromolecular protein preparations, or any components of serplulimab, or to paclitaxel or cisplatin or any components used in their preparations; 17. Diagnosed as any other malignant tumor before the first use of the investigational drug, excluding malignant tumors with low risk of metastasis and death (5-year survival rate\>90%), such as basal cell or squamous cell skin cancer or cervical cancer in situ that has been adequately treated; 18. According to the judgment of the researchers, the subjects may have other factors that may force them to terminate the study midway, such as having other serious illnesses (including mental illness) that require concurrent treatment, having other serious illnesses (such as myocardial infarction, cerebrovascular accident) in the near future, high risk of recurrence, severe abnormalities in laboratory test values, family or social factors, which may affect the safety of the subjects or the collection of trial data.

Where this trial is running

Nanjing, Jiangsu

• The First Affiliated Hospital of Nanjing Medical University — Nanjing, Jiangsu, China (Recruiting)

Conditions Esophageal Carcinoma; Serplulimab; Concurrent chemoradiotherapy