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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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.
• Процедура 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.

Первичные конечные точки

• Objective Response Rate [Срок оценки: 1 year]

Вторичные конечные точки (6)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

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

Идентификаторы

NCT: NCT07726446 · E20260847

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗