Safety and Efficacy of Multimodal Thermal Therapy (MTT) Combined With KRAS G12V mRNA Vaccine, S-1, and Sintilimab in Patients With Metastatic Pancreatic Cancer

Официальное название

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

Обзор

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.

Вмешательства

• Устройство Multimodal Thermal Therapy (MTT) System
  The MTT system is a medical device that performs sequential ablation therapy. Treatment consists of initial cryoablation followed immediately by radiofrequency ablation (RFA) to achieve a synergistic thermal effect against the tumor.
• Биопрепарат KRAS G12V mRNA Vaccine
  Administered via intramuscular injection at a dose of 1 mg. The first dose will be given 1 to 3 days after Multimodal Thermal Therapy (MTT). Subsequent doses will be administered every 3 weeks (Q3W) according to the study dosing schedule and clinical discretion.
• Препарат Sintilimab
  Administered via intravenous infusion at a dose of 200 mg on Day 1 (d1). Treatment will begin on 7 days after MTT and will be repeated every 3 weeks (Q3W) until disease progression or unacceptable toxicity.
• Препарат S-1
  Only participants aged \<80 years will receive oral S-1. Treatment starts on Day 7 after MTT at a dose of 40-60 mg twice daily (bid) on Days 1 to 14 (d1-14) of each cycle. Cycles are repeated every 3 weeks (Q3W) until disease progression or unacceptable toxicity.

Первичные конечные точки

• Incidence and Severity of Adverse Events (CTCAE v6.0) [Срок оценки: From the start of treatment up to 90 days after the last dose (or end of treatment).]
• Frequency of Dose Modifications and Treatment Discontinuations [Срок оценки: From the start of treatment up to 90 days after the last dose (or end of treatment).]

Вторичные конечные точки (2)

• Progression-Free Survival (RECIST 1.1) [Срок оценки: From the date of first study intervention until disease progression, death, or the last effective follow-up (up to approximately 24 months)]
• Overall Survival [Срок оценки: up to approximately 36 months]

Критерии участия

Критерии включения

• 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-C03:04.
• 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 1.
• Child-Pugh score ≤ 7 points.
• Expected overall survival of at least 3 months.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Ruijin Hospital, Shanghai Jiao Tong University School of Medicine — Шанхай

Идентификаторы

NCT: NCT07745790 · PLP1-13114

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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