Sodium bicarbonate, NASOX chemotherapy, and PD-1 immunotherapy delivered directly into the liver for pancreatic cancer metastases.

A Prospective, Single-Center, Phase II Clinical Study of Hepatic Arterial Infusion of Sodium Bicarbonate (NaHCO3) Combined With NASOX Regimen (Liposomal Irinotecan, Oxaliplatin, and S-1) Hepatic Arterial Infusion Chemotherapy (HAIC) and Intra-Arterial Programmed Death-1 (PD-1) Inhibitors for Liver Metastases From Pancreatic Cancer

This trial tests whether injecting sodium bicarbonate, a NASOX chemotherapy combination, and a PD-1 immune drug directly into the liver can help people whose pancreatic cancer has spread to the liver live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ruijin Hospital (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07504471 on ClinicalTrials.gov

What this trial studies

This single-center Phase II study enrolls adults with pathologically confirmed pancreatic ductal cancer and liver metastases to receive hepatic arterial infusion (HAIC) composed of sequential sodium bicarbonate, NASOX chemotherapy (oxaliplatin and liposomal irinotecan) and an intra-arterial PD-1 inhibitor, with oral S-1 as maintenance. The bicarbonate is infused first to neutralize tumor acidity, followed by chemotherapy and local immunotherapy to increase drug delivery and immune activation within liver lesions. Primary endpoint is overall survival compared to historical controls, with secondary endpoints including response rate, progression-free survival, and safety/tolerability. Interventions are performed by interventional radiology at Ruijin Hospital and patients must meet standard organ-function and performance-status criteria for enrollment.

Who should consider this trial

Good fit: Adults (≥18) with pathologically confirmed pancreatic ductal adenocarcinoma with liver metastases, ECOG 0–2, and adequate blood, liver, kidney, and cardiac function who can travel to Ruijin Hospital are ideal candidates.

Not a fit: Patients with poor performance status, significant extrahepatic disease, inadequate organ function, or who cannot undergo hepatic arterial infusion are unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could improve liver tumor control and overall survival by delivering higher local drug concentrations and enhancing immune response inside liver metastases.

How similar studies have performed: Prior studies of hepatic arterial infusion and combinations of chemotherapy with PD-1 inhibitors have shown some promising signals, but intra-arterial bicarbonate to neutralize tumor acidity is novel with limited clinical data.

Eligibility criteria

Inclusion Criteria:

* Aged 18 years and above, with no gender restrictions;
* Pathologically confirmed pancreatic cancer (originating from the pancreatic ductal epithelium), with metastasis to the liver;
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2;
* Adequate organ function, meeting the following criteria:

  a. Hematological tests:
  1. Neutrophils ≥ 1.5 × 10⁹ /L;
  2. White blood cells ≥ 3.0 × 10⁹ /L;
  3. Platelets ≥ 85 × 10⁹ /L;
  4. Hemoglobin ≥ 70 g/L; b. Biochemical tests:

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  1. Total bilirubin ≤ 2× upper limit of normal (ULN) (for subjects with biliary obstruction, after biliary drainage ≤ 2.5 × ULN);
  2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in metastatic subjects ≤ 5 × ULN;
  3. Albumin level ≥ 28 g/L;
  4. Creatinine clearance rate ≥ 60 ml/min; c. Cardiac function tests:

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  1. Normal electrocardiogram (ECG) or ECG abnormalities deemed clinically insignificant by the investigator;
  2. Left ventricular ejection fraction (LVEF) ≥ lower limit of normal;
* At least 3 weeks post-surgery, radiotherapy, chemotherapy, or other anti-tumor treatments, with general physical condition or related adverse reactions having recovered (toxicity ≤ grade 1) or stabilized;
* Willing to participate and sign the informed consent form;
* Good compliance and agreement to cooperate with survival follow-up.

Exclusion Criteria:

* Subjects with ascites requiring clinical intervention (including moderate to large amounts of ascites; subjects with ascites need to be stable for more than 4 weeks after drainage);
* Clinically severe gastrointestinal diseases (including bleeding, infectious inflammation, perforation, obstruction, or diarrhea greater than grade 1);
* NRS pain score ≥ 4 after standardized treatment with analgesics;
* Second primary malignancy within 5 years (except cured carcinoma in situ, basal cell, or squamous cell skin cancer; subjects with other previous tumors can be enrolled if there has been no recurrence within 5 years);
* Uncontrolled cardiovascular or cerebrovascular diseases with clinical symptoms, including but not limited to: ① NYHA class III or higher heart failure; ② unstable angina; ③ myocardial infarction or stroke within 6 months; ④ supraventricular or ventricular arrhythmias requiring treatment or intervention; ⑤ uncontrolled hypertension (systolic blood pressure \&gt; 150 mmHg and/or diastolic blood pressure \&gt; 90 mmHg despite optimal treatment);
* Known active hepatitis B subjects (HBsAg positive and HBV DNA ≥ 10³ copies or ≥ 1000 U/ml);
* Active infection or unexplained fever \&gt; 38.5°C during the screening period or on the day of administration (subjects with fever caused by tumors can be enrolled as judged by the investigator), which, in the investigator\&#39;s judgment, would affect the subject\&#39;s participation in this trial or interfere with the evaluation of efficacy;
* Pregnant or breastfeeding women;
* Women of childbearing potential with a positive blood (urine) pregnancy test during the screening period (both male and female subjects should use reliable contraception during the trial and for 3 months after the last dose to prevent pregnancy);
* Subjects with other medical or social issues that, in the investigator\&#39;s judgment, might affect their ability to sign informed consent, participation in the trial, or interpretation of the trial results;
* Patients with an estimated survival time of ≤ 3 months are not included in this study.

Where this trial is running

Shanghai, Shanghai Municipality

• Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Zhongmin Wang

Conditions Pancreatic Neoplasms; Hepatic Metastasis of Pancreatic Cancer