Study on Sequential Cryoablation, Relaforp Alpha, and Chemotherapy for Bile Duct Tumors

Summary

This study is a prospective, multicenter, single-arm, open-label Phase II clinical trial, planned to enroll 30 patients with unresectable locally advanced or metastatic iCCA/GBC. Patients will first receive cryoablation treatment, and two weeks after ablation, they will receive 8 cycles of immunotherapy combined with chemotherapy (Relatlimab α plus GC chemotherapy, every 3 weeks). During the maintenance phase, patients will continue with Relatlimab α alone, every 3 weeks, for up to one year. During the combination treatment phase, efficacy will be evaluated every 6 weeks, and during the maintenance phase, every 6 to 9 weeks. From the date of randomization/enrollment, survival follow-ups will be conducted every 3 months (±14 days) for the first 2 years; afterwards, follow-ups will occur every 6 months (±28 days) until the participant dies, is lost to follow-up, or the study ends, whichever comes first.

Eligibility

Inclusion Criteria:

1. Age ≥18 years, any gender;
2. Histologically confirmed unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma or gallbladder cancer;
3. No prior anti-tumor treatment;
4. At least one measurable target lesion according to RECIST 1.1 tumor evaluation criteria, and at least one lesion suitable for ablation;
5. No active autoimmune disease;
6. No concurrent malignancies;
7. ECOG performance status 0-1;
8. Expected survival ≥ 3 months;
9. Adequate organ and bone marrow function (no transfusion, recombinant human thrombopoietin, or colony-stimulating factor treatment within 2 weeks before first dose), defined as:

   1. Blood count: neutrophils (NEUT) ≥ 1.2×10\^9/L; platelets (PLT) ≥ 90×10\^9/L; hemoglobin ≥ 90 g/dL;
   2. Liver function: AST and ALT ≤ 2.5× upper limit of normal (ULN); ALP ≤ 2.5×ULN; total bilirubin (TBIL) ≤ 1.5×ULN; if liver metastases, ALT and AST ≤ 5×ULN;
   3. INR ≤ 1.25;
   4. Serum creatinine ≤ 1.5× ULN or creatinine clearance (CrCl) ≥ 30 mL/min (using Cockcroft-Gault formula);
10. Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use effective medical contraception from signing the informed consent until 6 months after the last dose;
11. Participants voluntarily join the study, sign the informed consent form, and can comply with scheduled visits and related procedures.

Exclusion Criteria:

1. Previously received systemic anti-tumor treatment;
2. Active brain metastases; patients with asymptomatic brain metastases can be enrolled; for patients clinically suspected of central nervous system metastasis, a CT or MRI must be performed within 28 days before enrollment to rule out central nervous system metastasis;
3. Had other malignant tumors within 5 years before administration (except tumors cured with radical treatment, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, cervical carcinoma in situ, etc.);
4. Allergic to the study drug (Rilafup Alpha Injection, or other immune checkpoint inhibitors);
5. History of unstable angina; newly diagnosed angina within 3 months before screening or myocardial infarction within 6 months before screening; arrhythmias (including QTcF: men ≥ 450 ms, women ≥ 470 ms) requiring long-term use of anti-arrhythmic drugs and NYHA class ≥ II heart failure;
6. Urinalysis showing protein ≥ and confirmed 24-hour urine protein quantification \> 1.0g;
7. Infectious pneumonia, non-infectious pneumonia, interstitial pneumonia, or other conditions requiring corticosteroid therapy; history of chronic autoimmune diseases, such as systemic lupus erythematosus; history of ulcerative colitis, Crohn's disease, or other inflammatory bowel diseases; history of chronic diarrhea conditions like irritable bowel syndrome; history of sarcoidosis or tuberculosis; active hepatitis B or C, and HIV infection;
8. Currently participating in interventional clinical research treatment, or have received other study drugs or devices within 4 weeks before first administration;
9. History of substance abuse that cannot be stopped or mental disorders; Any other situation in which the investigator believes the patient is not suitable for participation in this study.

Conditions2

Interventions1

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