Locally Advanced Pancreatic Cancer, Pancreatic Cancer
Conditions
Keywords
SCART, Radiotherapy, Dose Escalation, Phase I Trial
Brief summary
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).
Detailed description
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.
Interventions
RADIATIONSCART 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) using a standard 3+3 design. All patients will also receive background SBRT (25 Gy in 5 fractions) to the gross tumor volume and margin.
Sponsors
Shandong Cancer Hospital and Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label, single-arm dose-escalation study.
Intervention model description
This is a single-arm, phase I dose-escalation study using a standard 3+3 design to evaluate the safety and feasibility of SCART (Stereotactic Centralized Ablative Radiation Therapy) in patients with locally advanced pancreatic cancer.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
\- 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 0-1. Adequate bone marrow, liver, and renal function (per laboratory criteria). Life expectancy ≥ 3 months. Signed written informed consent prior to participation.
Exclusion criteria
\- 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | 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) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 12 months after enrollment | Overall survival will be defined as the time from the start of SCART treatment to death from any cause. Patients still alive at the time of analysis will be censored at the date of last follow-up. |
| Local Control Rate (LCR) | Up to 12 months after enrollment | Local tumor control will be assessed according to RECIST v1.1 criteria based on radiographic imaging (CT/MRI). Local control rate will be calculated as the proportion of patients without local progression. |
| Objective Response Rate (ORR) | Up to 12 months after enrollment | Objective tumor response will be evaluated using RECIST v1.1 criteria by imaging assessment. |
| Adverse Events (AEs) | Up to 12 months after enrollment | Incidence and severity of treatment-related adverse events (AEs) will be graded according to CTCAE v5.0 during and after radiotherapy. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORJinbo Yue, Doctor
Shandong Cancer Hospital and Institute
Outcome results
None listed