A Phase Ib/II Clinical Study of Regorafenib Combined With Toripalimab and Albumin-bound Paclitaxel for the Third-line Treatment of Advanced Pancreatic Cancer

Обзор

The purpose of this clinical trial is to explore the efficacy and safety of Regorafenib combined with Toripalimab and Paclitaxel-albumin in patients as the third line treatment for patients with unresectable or metastatic pancreatic cancer.The main question it aims to answer is: Phase Ib: Evaluate the maximum tolerated dose (MTD) of regorafenib and/or phase II clinical recommendations Dose (RP2D). Phase II: Evaluation of the efficacy and safety of Regorafenib Combined with Terriptylimab and Albumin Paclitaxel for Late Third Line Treatment for pancreatic cancer patients. Participants will: Phase Ib: Selected patients will receive treatment with Regorafenib at main dose levels of 40, 80, and 120mg/d (po d1-14 Q3W), Toripalimab(240mg, ivgtt, d1, Q3W), and Paclitaxel-albumi(125mg/m2, ivgtt, d1, 8, Q3W) until disease progression or intolerable toxicity occurs. Phase II: Regorafenib: Based on the results of the completed Phase I study, determine the dosage for Phase II (po d1-14 Q3W). Toripalimab (240mg, ivgtt, d1, Q3W) and Paclitaxel-albumi (125mg/m2, ivgtt, d1, 8, Q3W) until disease progression or intolerable toxicity occurs.

Вмешательства

• Препарат Regorafenib combined with Toripalimab and Albumin paclitaxel
  Regorafenib combined with Toripalimab and Albumin paclitaxel as the third line treatment for patients with advanced pancreatic cancer

Первичные конечные точки

• (PFS) [Срок оценки: Dated from the first treatment with study medication to the first documented PD or death owing to any cause, whichever occurred first,assessed up to 60 months.]

Вторичные конечные точки (2)

• ORR [Срок оценки: up to 60 months]
• OS [Срок оценки: Dated from the date of first treatment with study medication to the date of death owing to any cause or censored on the date of last follow-up,assessed up to 60 months.]

Критерии участия

Критерии включения

• The patient fully understands this study, voluntarily participates and signs an informed consent form (ICF);
• Age ≥ 18 years old and ≤ 80 years old;
• Patients with unresectable/metastatic pancreatic cancer confirmed by histopathology;
• Imaging confirmation of tumor progression after previous first-line and second-line standard treatment;
• According to RECIST 1.1 criteria, patients must have at least one measurable target lesion;
• Eastern Cancer Collaboration Group (ECOG) Physical Fitness Status Score: 0-2 points;
• Expected survival time ≥ 2 months;
• Absolute neutrophil count (ANC) ≥ 1.5 × 10 \^ 9/L, platelets ≥ 100 × 10 \^ 9/L, and hemoglobin ≥ 90 g/L (No blood transfusion or blood products within 14 days prior to laboratory examination.

Not treated with granulocyte colony-stimulating factor or other hematopoietic stimulating factors);

• Liver and kidney function: serum creatinine ≤ 1.5 times the upper limit of normal value; AST and ALT ≤ 2.5 times the upper limit of normal values (≤ 5 times the upper limit of normal values for patients with liver metastases); Total bilirubin ≤ 1.5 times the upper limit of normal value (≤ 3 times the upper limit of normal value for patients with liver metastasis);
• Women of childbearing age must undergo a pregnancy test (serum) within 7 days before enrollment, and the result must be negative, And willing to use appropriate contraception methods during the trial period and 6 months after the last administration of the trial drug.

Критерии исключения

• Have hypersensitivity reactions to any research drug or its components;
• Concurrent serious uncontrolled infections or other serious uncontrolled accompanying diseases, moderate or severe kidney injury; (such as progressive infection, uncontrollable hypertension, diabetes, etc.);
• Heart function and disease meet one of the following conditions:

• Long QTc syndrome or QTc interval>480 ms;
• Complete left bundle branch block, grade II or III atrioventricular block;
• Severe and uncontrolled arrhythmias requiring medication treatment;
• New York College of Cardiology classification ≥ III;
• Heart ejection fraction (LVEF) below 50%;
• History of myocardial infarction, unstable angina, and severe unstable ventricular arrhythmia within 6 months prior to recruitment or any other arrhythmia requiring treatment, history of clinically severe pericardial disease, or there may be electrocardiographic evidence of acute ischemic or active conduction system abnormalities.
• Active infection of hepatitis B and C (hepatitis B virus surface antigen is positive and hepatitis B virus DNA exceeds 1x103 copies/mL; Hepatitis C virus RNA exceeding 1x103 copies/mL).Asymptomatic chronic carriers of hepatitis B or hepatitis C excluded;
• Human immunodeficiency virus (HIV) infection (HIV antibody positive);
• Imaging confirms intestinal obstruction;
• Previously or currently suffering from other malignant tumors simultaneously (Except for non melanoma basal cell carcinoma and breast/cervical carcinoma in situ that have been effectively controlled and other malignant tumors that have been effectively controlled without treatment in the past five years);
• Pregnant and lactating women, as well as reproductive age patients who are unwilling to take contraceptive measures;
• Patients who require treatment for merging with other malignant tumors;
• History of pulmonary hemorrhage/hemoptysis ≥ grade 2 (defined as at least 2.5mL of bright red blood) within one month prior to the first administration;
• Within 6 months prior to the first administration, there are arterial embolism, severe bleeding (excluding bleeding caused by surgery), and a tendency for severe bleeding;
• Merge symptomatic brain metastases, meningeal metastases, spinal cord tumor invasion, and spinal cord compression syndrome;
• Have used other clinical trial drugs within one month before the first administration;
• The researchers have determined that patients who are not suitable to participate 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

• Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center — Шэньчжэнь

Идентификаторы

NCT: NCT07040228 · YW2025-28-1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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