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

Official title

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

Overview

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.

Interventions

• 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.

Primary outcome measures

• Objective Response Rate [Time frame: 1 year]

Secondary outcome measures (6)

• Objective response rate in the subgroup [Time frame: 1 year]
• disease control rate [Time frame: 1 year]
• Progression-free survival [Time frame: 2 years]
• Overall survival [Time frame: 2 years]
• Duration of Response [Time frame: 1 year]
• mRECIST standard evaluation of objective response rate [Time frame: 1 year]

Eligibility criteria

Inclusion criteria

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

• Blood count: neutrophils (NEUT) ≥ 1.2×10\^9/L; platelets (PLT) ≥ 90×10\^9/L; hemoglobin ≥ 90 g/dL;
• 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;
• INR ≤ 1.25;
• Serum creatinine ≤ 1.5× ULN or creatinine clearance (CrCl) ≥ 30 mL/min (using Cockcroft-Gault formula);
• 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;
• Participants voluntarily join the study, sign the informed consent form, and can comply with scheduled visits and related procedures.

Exclusion criteria

• Previously received systemic anti-tumor treatment;
• 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;
• 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.);
• Allergic to the study drug (Rilafup Alpha Injection, or other immune checkpoint inhibitors);
• 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;
• Urinalysis showing protein ≥ and confirmed 24-hour urine protein quantification > 1.0g;
• 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;
• Currently participating in interventional clinical research treatment, or have received other study drugs or devices within 4 weeks before first administration;
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, — Tianjin

Identifiers

NCT: NCT07726446 · E20260847

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗