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

Safety and Effectiveness of Sequential Cryoablation With Rilafup α and Chemotherapy as First-line Treatment for Intrahepatic Cholangiocarcinoma and Gallbladder Cancer: a Multicenter, Prospective, Single-arm, Phase II Clinical Study

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.

Study Overview

• Status: Recruiting
• Conditions: Biliary Tract Cancer (BTC)
• Intervention / Treatment: Drug: PD-1 and chemotherapy; Procedure: cryoablation

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tianqiang T Song, MD; Phone Number: 18622221077; Email: tjchi@hotmail.com
• Study Contact Backup: Name: Liyu L Sun; Phone Number: 17860489096

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Recruiting
      • Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
      • Contact: Tianqiang T Song, MD; Phone Number: 18622221077; Email: tjchi@hotmail.com
      • Contact: Liyu L Sun; Phone Number: 17860489096

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ablation combined with chemo and immunotherapy

Drug: PD-1 and chemotherapy; Rilapafup α: 1800 mg, intravenous infusion, every 3 weeks. Use Rilapafup α injection (same dose as above) for maintenance therapy until disease progression or unacceptable toxicity occurs. Chemotherapy: Gemcitabine 1000 mg/m² IV infusion over 30 minutes on days 1 and 8; Cisplatin 25 mg/m² IV infusion on days 1 and 8; repeat every 3 weeks.; Procedure: cryoablation; Cryoablation: Depending on the size and location of the tumor, a cryoprobe is inserted percutaneously into the center of the tumor under ultrasound guidance. Once the probe is in place, the tip is cooled down to -196℃, freezing the tumor for 15 minutes, then warmed up (to about 80℃) for 5 minutes, completing two freeze-thaw cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	ORR	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	2 years
Progression-free survival	2 years
disease control rate	1 year
Duration of Response	1 year
Objective response rate in the subgroup	1 year
mRECIST standard evaluation of objective response rate	1 year

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: July 15, 2026
• First Submitted That Met QC Criteria: July 22, 2026
• First Posted (Actual): July 24, 2026

Study Record Updates

• Last Update Posted (Actual): July 24, 2026
• Last Update Submitted That Met QC Criteria: July 22, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Biliary Tract Diseases; Biliary Tract Neoplasms; Therapeutics; Surgical Procedures, Operative; Ablation Techniques; Drug Therapy; Cryosurgery
• Other Study ID Numbers: E20260847

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No