A Study of Multimodal Thermal Therapy (MTT) Combined With KRAS G12V mRNA Vaccine, S-1, and Sintilimab for Safety and Efficacy in Patients With Metastatic Pancreatic Ductal Adenocarcinoma Who Have Disease Progression After or Are Intolerant to Standard First-Line Therapy
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Incidence and Severity of Adverse Events (CTCAE v6.0)
研究概览
简要总结
This is a single-arm, single-center, exploratory clinical study. A total of 20 participants with metastatic pancreatic ductal adenocarcinoma (with liver or lung metastasis) who have experienced disease progression after or are intolerant to standard first-line chemotherapy (based on the AG regimen [Albumin-bound Paclitaxel plus Gemcitabine]) will be enrolled.The study aims to evaluate the safety, efficacy, and underlying immunological mechanisms of Multimodal Thermal Therapy (MTT) combined with a KRAS G12V mRNA vaccine, S-1, and Sintilimab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged ≥ 18 years old with no restriction on gender.
- •Patients with advanced pancreatic cancer or postoperative recurrent pancreatic cancer confirmed by histopathological or cytological examination.
- •Tumor tissues are confirmed to carry KRAS G12V mutation via sequencing and bioinformatics analysis (valid test reports obtained within the previous 12 months and recognized by the investigator are acceptable). In the dose expansion phase, patients must harbor at least one HLA allele capable of effectively presenting the corresponding antigen, including HLA-A11:01, HLA-A03:01, HLA-A30:01, HLA-A68:01, HLA-C01:02, HLA-C03:03, and HLA-C03:
- •Disease resistance or intolerance to prior AG-based chemotherapy regimens.
- •Presence of liver metastasis or lung metastasis.
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or
- •Child-Pugh score ≤ 7 points.
- •Expected overall survival of at least 3 months.
排除标准
- •Presence of diffuse hepatic or pulmonary metastases.
- •Prior local treatment including radiofrequency ablation, microwave ablation, radiotherapy or other local therapies for metastatic lesions.
- •Current participation in other interventional clinical studies and receiving investigational treatment.
- •Diagnosis of any other malignant disease within 5 years prior to the first study drug administration (excluding radically treated basal cell carcinoma, squamous cell carcinoma of the skin, and/or radically resected in situ carcinoma).
- •Prior history of solid organ or hematopoietic stem cell transplantation.
- •Any disease requiring systemic treatment with corticosteroids (prednisone or equivalent daily dose > 10 mg) or other immunosuppressive agents within 14 days prior to enrollment.
- •Previous or current diagnosis of brain metastases with incompletely controlled symptoms (i.e., persistent or aggravated symptoms, or requirement for adjusted symptomatic treatment to maintain symptom relief).
- •Presence of uncontrolled active infection.
- •Renal dysfunction defined as serum creatinine > 176.8 μmol/L or creatinine clearance < 30 mL/min.
- •Uncorrectable coagulation abnormalities, including platelet count < 50×10⁹/L, prothrombin time > 18 seconds, or prothrombin activity < 40%, which cannot be corrected.
- •History of esophagogastric variceal rupture without effective treatment via endoscopy, interventional therapy or surgery.
- •Patients with psychiatric disorders in the acute episode stage.
- •Women of childbearing potential who are pregnant, breastfeeding, or planning to become pregnant during the study treatment period or within 3 months after the end of study treatment.
- •Prior systemic pharmacotherapy, radiotherapy or local hepatic treatment with an interval of < 1 month from the last systemic or local hepatic treatment to the first study drug administration.
结局指标
主要结局
Incidence and Severity of Adverse Events (CTCAE v6.0)
时间窗: From the start of treatment up to 90 days after the last dose (or end of treatment).
To assess the safety profile of the combination regimen (MTT + KRAS G12V mRNA vaccine + Sintilimab ± S-1) in patients with metastatic pancreatic cancer. Safety will be evaluated by recording the incidence, type, and maximum grade of adverse events (AEs) and serious adverse events (SAEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0.
Frequency of Dose Modifications and Treatment Discontinuations
时间窗: From the start of treatment up to 90 days after the last dose (or end of treatment).
To evaluate patient tolerability to the multimodal regimen. Tolerability is defined as the ability of participants to receive the full planned treatment. Specifically, it measures the proportion of participants requiring dose modifications, treatment delays, treatment interruptions, or permanent discontinuation of any component of the therapy (MTT, S-1 \[for those \<80 years\], Sintilimab, or mRNA vaccine) due to adverse events.
次要结局
- Progression-Free Survival (RECIST 1.1)(From the date of first study intervention until disease progression, death, or the last effective follow-up (up to approximately 24 months))
- Overall Survival(up to approximately 36 months)