LDRT and Chemoimmunotherapy in NPC With Liver Metastasis

Официальное название

Low-dose Radiotherapy and Chemoimmunotherapy in Nasopharyngeal Carcinoma With Liver Metastasis

Обзор

This study aims to evaluate the efficacy and toxicity of adding low-dose radiotherapy to chemoimmunotherapy as a first-line treatment for nasopharyngeal carcinoma patients with liver metastasis.

Подробное описание

Low-dose radiotherapy to the liver metastasis. Chemotherapy: gemcitabine and cisplatin Immunotherapy: penpulimab

Вмешательства

• Другое Low-dose radiotherapy combine with chemoimmunotherapy
  Radiation: 1.4Gy for 5 days to the liver metastasis before chemoimmunotherapy. Chemoimmunotherapy: gemcitabine(1000mg per square meter on days 1,8) , cisplatin (80mg per square meter on day 1), penpulimab (200mg, day1)

Первичные конечные точки

• Intrahepatic progression-free survival (iPFS) [Срок оценки: 1 year]

Вторичные конечные точки (4)

• Progression-free survival (PFS) [Срок оценки: 1 year]
• Overall survival (OS) [Срок оценки: 2 year]
• Objective response rate (ORR) [Срок оценки: 18 weeks]
• Incidence rate of adverse events (AEs) [Срок оценки: 2 year]

Критерии участия

Критерии включения

• Age ≥ 18 years and ≤ 70 years, male or non-pregnant female.
• Histologically confirmed with nonkeratinizing carcinoma of the nasopharynx (differentiated or undifferentiated type, WHO II or III)
• Stage IVB (AJCC 8th edition staging)
• De novo nasopharyngeal carcinoma with liver metastasis, or patients who had received curative treatment (radical radiotherapy or radical radiotherapy combined with chemotherapy) and developed liver metastasis more than 6 months after treatment completion.
• ECOG performance status: 0 or 1
• Must have at least one measurable lesion (assessed according to RECIST v1.1)
• Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L; platelets ≥ 100 × 10\^9/L; hemoglobin ≥ 90 g/L.
• International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × upper limit of normal (ULN); activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN
• Serum creatinine ≤ 1.5 × ULN or estimated glomerular filtration rate (eGFR) ≥ 60 mL/min.
• Serum total bilirubin ≤ 1.5 × ULN (patients with Gilbert's syndrome may be included if total bilirubin < 3 × ULN); AST and ALT ≤ 5 × ULN （because of liver metastasis）

Критерии исключения

• Patients with tumor recurrence at the primary site who have previously received radical radiotherapy.
• Tumor invasion involving major blood vessels, with a high risk of significant bleeding as assessed by the investigator.
• Systemic anticancer therapy, including hormone therapy, administered within 28 days prior to the initiation of the study treatment.
• Previous treatment with immune checkpoint inhibitors (e.g., PD-1/PD-L1, CTLA-4).
• Patients with active autoimmune diseases or a history of autoimmune diseases with a risk of recurrence.
• Known history of other malignancies (except cured basal cell carcinoma or carcinoma in situ of the cervix).
• Conditions requiring systemic corticosteroid therapy (equivalent to >10 mg/day of prednisone or similar medications) or other immunosuppressive therapy within ≤14 days prior to treatment.
• Uncontrolled diabetes or laboratory abnormalities ≥Grade 1 in potassium, sodium, or corrected calcium levels despite standard treatment, or ≥Grade 3 hypoalbuminemia within ≤14 days before treatment.
• History of the following diseases: interstitial lung disease, non-infectious pneumonitis, or uncontrolled diseases, including pulmonary fibrosis or acute lung disease.
• Severe chronic or active infections requiring systemic antibiotics, antifungals, or antivirals within ≤14 days before the first dose of the investigational drug (including tuberculosis infection).
• Known history of HIV infection.
• Untreated chronic hepatitis B patients or hepatitis B virus (HBV) carriers with HBV DNA ≥500 IU/mL, or active hepatitis C virus (HCV) carriers.
• Any major surgery requiring general anesthesia within ≤28 days prior to treatment.
• Previous allogeneic stem cell transplantation or organ transplantation.
• Any cardiovascular risk factors, including: cardiac chest pain that restricts daily instrumental activities ≤28 days before treatment. Symptomatic pulmonary embolism within ≤3 months before treatment. Acute myocardial infarction within ≤6 months before treatment. History of heart failure meeting New York Heart Association (NYHA) Class III or IV within ≤6 months before treatment. Grade ≥2 ventricular arrhythmias within ≤6 months before treatment. History of cerebrovascular accident within ≤6 months before the first dose of the investigational drug.
• Evident bleeding tendencies or clinically significant bleeding symptoms ≤28 days prior to randomization, including but not limited to gastrointestinal bleeding, nasal bleeding (excluding epistaxis or retrograde blood-stained nasal discharge), and persistent bleeding disorders or coagulopathy.
• Known allergy to any component of the investigational drug or a history of severe hypersensitivity to other monoclonal antibodies.
• Peripheral neuropathy of Grade ≥2 as defined by NCI CTCAE v5.0.
• Administration of live vaccines within ≤4 weeks prior to treatment.
• Underlying medical conditions (including laboratory abnormalities) or alcohol/drug abuse or dependency that could impair drug administration, interpretation of drug toxicity, or adverse events (AEs), or could compromise study compliance or execution.
• Pregnant or breastfeeding women.
• Other factors deemed by the investigator that could lead to the premature termination of the study, such as other severe illnesses, significant laboratory abnormalities, or family/social factors that could affect participant safety or the collection of study data.

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 · 8 центров

• Third Xiangya Hospital, Central South University, — Чанша
• Xiangya Hospital of Central South University — Чанша
• Hunan Cancer Hospital — Чанша
• Hunan Cancer Hospital — Чанша
• The First People's Hospital of Chenzhou — Chenzhou
• Hunan University of Medicine General Hospital — Huaihua
• The Central Hospital of Shaoyang — Shaoyang
• Yueyang Central Hospital — Yueyang

Идентификаторы

NCT: NCT06788002 · KY2024528 · Z2023080

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗