Clinical Study of Radiotherapy Combined With Adebrelimab and NALIRIFOX for Conversion Therapy in Locally Advanced Pancreatic Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 36
- 主要终点
- surgical conversion rate
研究概览
简要总结
This study intends to explore conversion therapy for locally advanced pancreatic cancer (LAPC). The intervention starts with modified stereotactic body radiation therapy (3-day regimen), followed by systemic therapy within 1-2 weeks after irradiation. Subsequently, the investigator will evaluate the resectability of the lesion.
For subjects converted to resectable status, surgical resection will be performed, followed by postoperative adjuvant therapy.
For subjects who remain unresectable but maintain stable disease, a second cycle of conversion therapy will be continued. If the lesion is converted to resectable, surgical resection will be performed followed by adjuvant therapy. If disease progression occurs, subsequent treatment will be carried out in accordance with the first-line treatment for advanced pancreatic cancer.
For subjects who experience disease progression or distant metastasis, subsequent treatment will be administered by adjusting the chemotherapy regimen in accordance with the first-line standard regimen for advanced pancreatic cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent form
- •Age 18-75 years
- •Histologically or cytologically confirmed pancreatic ductal adenocarcinoma
- •Locally advanced disease as determined by the investigator (with reference to the CSCO Clinical Practice Guidelines for Pancreatic Cancer)
- •No prior treatment for pancreatic cancer, including radiotherapy, chemotherapy, or surgery
- •At least one measurable lesion according to RECIST v1.1 criteria
- •ECOG performance status score of 0-1
- •Adequate organ function based on laboratory tests performed within 28 days prior to the first dose:
- •Complete blood count:
- •Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L Platelet count ≥ 75 × 10⁹/L Hemoglobin ≥ 90 g/L
- •Blood biochemistry:
- •Serum albumin ≥ 30 g/L Serum total bilirubin ≤ 1.5 × ULN ALT and AST ≤ 3 × ULN Serum creatinine (Cr) ≤ 1.5 × ULN; or creatinine clearance calculated by the Cockcroft-Gault formula > 50 mL/min
- •International normalized ratio (INR) ≤ 1.2, or prothrombin time (PT) exceeding the normal range by ≤ 2 seconds
- •Urine protein < 2+ (if urine protein ≥ 2+, 24-hour urine protein quantification is required; patients with 24-hour urine protein < 1.0 g are eligible) Male subjects and female subjects of childbearing potential must use contraceptive measures from the first dose until 6 months after the last dose of the study drug
排除标准
- •Presence of distant metastasis
- •Contraindications to surgical resection of pancreatic cancer
- •History of another malignancy other than pancreatic cancer within 5 years prior to enrollment, or concurrent malignancy at the time of enrollment
- •Prior allogeneic stem cell transplantation or solid organ transplantation
- •Symptomatic active central nervous system (CNS) metastases and/or carcinomatous meningitis, or uncontrolled major seizure disorder, unless ruled out by CT or MRI
- •History of uncorrectable electrolyte disturbances, including serum potassium, calcium, or magnesium abnormalities
- •Current interstitial pneumonia or interstitial lung disease, history of interstitial pneumonia or interstitial lung disease requiring corticosteroid therapy, or any other condition that may interfere with the assessment and management of immune-related pulmonary toxicity; active pulmonary tuberculosis
- •Active autoimmune disease or history of autoimmune disease with potential for recurrence
- •Use of immunosuppressive agents or systemic corticosteroids for the purpose of immunosuppression within 2 weeks prior to enrollment
- •Active infection, unexplained fever ≥ 38.5°C within 1 week prior to enrollment, or baseline white blood cell count > 15 × 10⁹/L; use of oral or intravenous therapeutic antibiotics within 2 weeks prior to enrollment
- •Congenital or acquired immunodeficiency (e.g., HIV infection)
- •Receipt of a live attenuated vaccine within 4 weeks prior to enrollment, or anticipated need for such vaccination during adebrelimab treatment or within 60 days after the last dose
- •Clinically significant bleeding symptoms or evident bleeding tendency within 6 months prior to enrollment; known hereditary or acquired bleeding tendency or thrombotic tendency
- •Major vascular disease, arterial thromboembolism
- •Uncontrolled or poorly controlled cardiac clinical symptoms or disease, such as:
- •New York Heart Association (NYHA) Class > II heart failure, or left ventricular ejection fraction (LVEF) < 50% as assessed by color Doppler echocardiography
- •Unstable angina pectoris
- •Myocardial infarction within 1 year prior to initiation of study treatment
- •Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention
- •QTc interval > 450 ms (males) or > 470 ms (females) (QTc calculated using Fridericia's formula; if the QTc value is abnormal, measurements should be repeated three times at 2-minute intervals and the average value taken) Uncontrolled pleural effusion, pericardial effusion, or moderate or greater ascites
- •Hypertension not adequately controlled with antihypertensive medication (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg); history of hypertensive crisis or hypertensive encephalopathy
- •Presence of severe, non-healing or dehisced wounds, active ulcers, or untreated fractures
- •Major surgery (excluding diagnostic surgery) within 4 weeks prior to enrollment, or planned major surgery during the study period
- •History of intestinal obstruction and/or clinical symptoms or signs of gastrointestinal obstruction within 6 months prior to enrollment
- •Known allergy or hypersensitivity to any study drug or excipient
- •Participation in another clinical study of an investigational drug within 4 weeks prior to enrollment
- •Pregnant or breastfeeding women
- •Other factors that, in the opinion of the investigator, render the subject unsuitable for study participation
研究组 & 干预措施
LPAC+NALIRIFOX+Adebrelimab
The intervention starts with modified stereotactic body radiation therapy (3-day regimen), followed by systemic therapy within 1-2 weeks after irradiation. Subsequently, the investigator will evaluate the resectability of the lesion.
For subjects converted to resectable status, surgical resection will be performed, followed by postoperative adjuvant therapy.
For subjects who remain unresectable but maintain stable disease, a second cycle of conversion therapy will be continued. If the lesion is converted to resectable, surgical resection will be performed followed by adjuvant therapy. If disease progression occurs, subsequent treatment will be carried out in accordance with the first-line treatment for advanced pancreatic cancer.
For subjects who experience disease progression or distant metastasis, subsequent treatment will be administered by adjusting the chemotherapy regimen in accordance with the first-line standard regimen for advanced pancreatic cancer.
干预措施: Adebrelimab (PD-L1 inhibitor) (Drug)
LPAC+NALIRIFOX+Adebrelimab
The intervention starts with modified stereotactic body radiation therapy (3-day regimen), followed by systemic therapy within 1-2 weeks after irradiation. Subsequently, the investigator will evaluate the resectability of the lesion.
For subjects converted to resectable status, surgical resection will be performed, followed by postoperative adjuvant therapy.
For subjects who remain unresectable but maintain stable disease, a second cycle of conversion therapy will be continued. If the lesion is converted to resectable, surgical resection will be performed followed by adjuvant therapy. If disease progression occurs, subsequent treatment will be carried out in accordance with the first-line treatment for advanced pancreatic cancer.
For subjects who experience disease progression or distant metastasis, subsequent treatment will be administered by adjusting the chemotherapy regimen in accordance with the first-line standard regimen for advanced pancreatic cancer.
干预措施: NALIRIFOX (Drug)
LPAC+NALIRIFOX+Adebrelimab
The intervention starts with modified stereotactic body radiation therapy (3-day regimen), followed by systemic therapy within 1-2 weeks after irradiation. Subsequently, the investigator will evaluate the resectability of the lesion.
For subjects converted to resectable status, surgical resection will be performed, followed by postoperative adjuvant therapy.
For subjects who remain unresectable but maintain stable disease, a second cycle of conversion therapy will be continued. If the lesion is converted to resectable, surgical resection will be performed followed by adjuvant therapy. If disease progression occurs, subsequent treatment will be carried out in accordance with the first-line treatment for advanced pancreatic cancer.
For subjects who experience disease progression or distant metastasis, subsequent treatment will be administered by adjusting the chemotherapy regimen in accordance with the first-line standard regimen for advanced pancreatic cancer.
干预措施: SBRT (Radiation)
结局指标
主要结局
surgical conversion rate
时间窗: 3 years
The proportion of patients who become eligible for surgery after treatment, relative to the total number of patients.
次要结局
- pCR(in 3 years)
- R0/R1 Resection Rate(in 3 years)
- MPR(in 3 years)
- ORR(in 3 years)
- EFS(in 3 years)
- OS(in 3 years)
- the incidence, severity, and relationship to study treatment of adverse events (AEs) and serious adverse events (SAEs)(in 3 years)
- Immune Age Rejuvenation(in 3 years)
研究者
Jiang Long
Chief Physician
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine