Liver Neoplasms, Lung Neoplasms, Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
Multimodal Thermal Therapy, mRNA, Metastatic Pancreatic Cancer
Brief summary
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.
Interventions
DEVICEMultimodal 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.
BIOLOGICALKRAS 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.
DRUGSintilimab
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.
DRUGS-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.
Sponsors
Ruijin Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Adverse Events (CTCAE v6.0) | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Time from the date of first study intervention to the date of radiographic disease progression per RECIST version 1.1, death from any cause, or the date of the last effective follow-up. Radiographic assessments will be performed every 1-2 months using contrast-enhanced abdominal MRI or CT imaging. |
| Overall Survival | up to approximately 36 months | Time from the date of first study intervention to the date of death from any cause or the date of the last confirmed survival follow-up. Long-term survival will be tracked through regular follow-up visits until death, loss to follow-up, or study termination. |
Countries
China
Contacts
CONTACTbaiyong shen
Outcome results
None listed