Stereotactic Centralized Ablative Radiotherapy for Locally Advanced Pancreatic Cancer: A Single-Arm Phase I Safety and Feasibility Study
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
This is a single-arm, phase I clinical study designed to evaluate the safety and feasibility of SCART (Stereotactic Centralized Ablative Radiation Therapy) dose escalation in patients with locally advanced pancreatic cancer. Pancreatic cancer carries a dismal prognosis, and the majority of patients are not surgical candidates at diagnosis. Radiotherapy is an important local treatment modality, but conventional approaches have shown limited efficacy. SCART is intended to deliver higher ablative doses to the tumor core while minimizing toxicity to surrounding normal tissues. In this trial, eligible patients will receive SCART with escalating dose levels using a standard 3+3 design. The primary endpoints are to determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD). Secondary endpoints include overall survival (OS), local control rate (LCR), and objective response rate (ORR).
详细描述
Pancreatic cancer is among the most aggressive malignancies and is associated with poor prognosis. The 5-year survival rate remains below 10%, and most patients present with unresectable disease at diagnosis. Radiotherapy plays a pivotal role in local disease control, yet conventional fractionated radiotherapy (CFRT) has demonstrated limited survival benefits. Stereotactic body radiotherapy (SBRT) allows delivery of higher biologically effective doses with improved local control, but further dose escalation is restricted by normal tissue tolerance.
SCART (Stereotactic Centralized Ablative Radiation Therapy) is an innovative technique that delivers ablative radiation doses to selected intratumoral sub-volumes while maintaining lower doses at the tumor periphery. This spatial dose distribution has the potential to induce bystander effects and enhance biological efficacy beyond that achievable with uniform SBRT.
This phase I study is designed to evaluate the safety and feasibility of SCART dose escalation in patients with locally advanced pancreatic cancer. Patients will be enrolled into sequential dose cohorts (10 Gy, 13 Gy, 16 Gy, and 19 Gy per fraction within the SCART region) using a standard 3+3 dose-escalation design. All patients will also receive background SBRT (25 Gy in 5 fractions) covering the gross tumor volume and margin.
The primary objective is to determine dose-limiting toxicities (DLTs) and establish the maximum tolerated dose (MTD) of SCART. Secondary objectives include overall survival (OS), local control rate (LCR), objective response rate (ORR), and treatment-related adverse events (AEs). Exploratory analyses will investigate potential biomarkers and immune response modulation associated with SCART.
The estimated enrollment is 12-24 patients, with an accrual period of 24 months and a minimum follow-up of 12 months.
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
盲法说明
This is an open-label, single-arm dose-escalation study.
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •- Age 18-70 years, male or female. Histologically or cytologically confirmed diagnosis of pancreatic cancer. Locally advanced, unresectable disease without evidence of distant metastasis (based on imaging such as CT/MRI/PET-CT).
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Adequate bone marrow, liver, and renal function (per laboratory criteria). Life expectancy ≥ 3 months. Signed written informed consent prior to participation.
排除标准
- •- Evidence of distant metastasis. Prior abdominal radiotherapy. Prior systemic chemotherapy or immunotherapy within 4 weeks before enrollment. Concurrent participation in another interventional clinical trial. Severe comorbidities (e.g., uncontrolled cardiovascular, pulmonary, or infectious diseases).
- •Pregnant or breastfeeding women. Known history of other malignancies within the past 5 years (except adequately treated basal cell carcinoma of the skin or cervical carcinoma in situ).
- •Any condition that, in the investigator's judgment, would interfere with patient safety or compliance with the study protocol.
研究组 & 干预措施
SCART Dose Escalation Arm
Patients will receive SCART with escalating dose cohorts (10 Gy, 13 Gy, 16 Gy, and 19 Gy per fraction within the SCART region).
干预措施: SCART Dose Escalation Arm (Radiation)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: Within 90 days after completion of radiotherapy
The maximum tolerated dose (MTD) of SCART (Stereotactic Centralized Ablative Radiation Therapy) will be determined using a standard 3+3 dose-escalation design. MTD is defined as the highest dose level at which the incidence of dose-limiting toxicities (DLTs), graded according to CTCAE v5.0, does not exceed 33% of patients in that cohort.
Dose-Limiting Toxicities (DLTs)
时间窗: Within 90 days after completion of radiotherapy
Incidence of dose-limiting toxicities (DLTs) graded according to the National Cancer Institute Common Terminology CTCAE v5.0. DLTs will be evaluated during the dose-escalation phase to assess the safety of SCART (Stereotactic Centralized Ablative Radiation Therapy).
次要结局
- Overall Survival (OS)(Up to 12 months after enrollment)
- Local Control Rate (LCR)(Up to 12 months after enrollment)
- Objective Response Rate (ORR)(Up to 12 months after enrollment)
- Adverse Events (AEs)(Up to 12 months after enrollment)
研究者
Jinbo Yue
Director of Department Radiation Oncology
Shandong Cancer Hospital and Institute