Overview
This is a Phase II, multicenter, randomized controlled trial to assess the efficacy of Stereotactic Body Radiotherapy (SBRT) in combination with maintenance therapy in patients with advanced pancreatic cancer. The aim is to compare the efficacy of SBRT combined with maintenance therapy versus maintenance therapy alone. The primary outcome is the overall survival (OS) of patients, with secondary endpoints including progression-free survival (PFS), response rates, and quality of life assessments. The study will involve patients with unresectable pancreatic adenocarcinoma who are receiving chemotherapy and have stable disease. The hypothesis is that SBRT, by improving local control, can enhance the benefit of ongoing maintenance therapy and lead to better overall survival outcomes in this patient group.
Description
Pancreatic cancer is one of the most aggressive malignancies, and most patients are diagnosed at an advanced stage, making them ineligible for surgery. Despite systemic chemotherapy being the standard treatment for advanced pancreatic cancer, the prognosis remains poor, with median survival often less than one year. The addition of radiotherapy has shown some promise in improving outcomes, particularly in the setting of local control.
This Phase II, multicenter, randomized controlled trial evaluates the combination of Stereotactic Body Radiotherapy (SBRT) with maintenance therapy versus maintenance therapy alone in patients with advanced pancreatic cancer. SBRT offers a high dose of radiation with minimal damage to surrounding healthy tissues, potentially enhancing tumor control while preserving immune function, a key challenge in pancreatic cancer treatment. Moreover, SBRT has shown potential in stimulating anti-tumor immune responses, thus converting "cold" tumors into "hot" tumors that may respond better to subsequent therapies.
Patients eligible for this trial will have completed at least four months of first-line chemotherapy, achieving stable disease (SD) or partial response (PR) according to RECIST 1.1 criteria. After completion of the chemotherapy, they will be randomized into two groups: the experimental group will receive SBRT in addition to maintenance chemotherapy, while the control group will receive maintenance chemotherapy alone. The chemotherapy regimen will be based on the patient's first-line treatment.
The study will evaluate the primary endpoint of one-year overall survival (OS) rate, alongside secondary endpoints including overall survival, progression-free survival (PFS), local control rate (LCR), and adverse event (AE) rates. In addition, exploratory endpoints include identifying potential biomarkers associated with the anti-tumor efficacy of SBRT and maintenance therapy. These biomarkers include PD-L1 expression, tumor mutational burden (TMB), and changes in immune cell subsets in blood and tumor tissue.
The results of this study will provide valuable insights into the combination of SBRT and maintenance chemotherapy as a potential treatment option for advanced pancreatic cancer, which may lead to improved survival outcomes and a better understanding of the biological mechanisms that drive treatment response.
Eligibility
Inclusion Criteria:
- Age 18 to 70 years old.
- Histologically or cytologically confirmed diagnosis of pancreatic - adenocarcinoma.
- No prior radiation therapy for pancreatic cancer.
- At least one measurable lesion of the primary pancreatic tumor as per RECIST 1.1 criteria, eligible for SBRT.
- Completion of first-line chemotherapy with stable disease (SD) or partial response (PR) after ≥4 months of treatment.
- ECOG performance status of 0-2.
- Expected survival of ≥3 months.
- Adequate organ function within 14 days prior to enrollment:
- Hemoglobin (Hb) ≥ 90 g/L
- Absolute neutrophil count (ANC) ≥ 1.5×10⁹/L
- Platelets (PLT) ≥ 75×10⁹/L
- Total bilirubin ≤ 1.5× ULN or direct bilirubin ≤ ULN
- ALT/AST ≤ 2.5× ULN
- ALP ≤ 2.5× ULN
- Serum creatinine ≤ 1.5× ULN or calculated creatinine clearance ≥ 40 mL/min
- Urine protein \< 2+ (if ≥2+ on dipstick, 24-hour urine protein must be \< 2g)
- No use of systemic corticosteroids in the last 7 days prior to enrollment (physiological corticosteroid replacement is allowed).
- Women of childbearing potential and men must use effective contraception during the study and for 12 months following treatment completion.
- Voluntary participation with signed informed consent.
- Ability to comply with the study schedule.
Exclusion Criteria:
- Currently participating in any interventional clinical trial or having received other investigational drugs or devices within 4 weeks prior to enrollment.
- Peritoneal metastasis.
- Known active central nervous system (CNS) metastasis and/or carcinomatous meningitis.
- Receiving systemic corticosteroid treatment within 7 days prior to enrollment (except for physiological doses).
- Active, untreated hepatitis B (HBsAg positive and detectable HBV-DNA) or active hepatitis C infection (HCV antibody positive and detectable HCV RNA).
- Pregnant or breastfeeding women.
- Any severe or uncontrolled systemic disease, including:
- QTc interval ≥ 480 ms
- Unstable angina
- NYHA class III-IV congestive heart failure
- Arterial thromboembolism (MI, unstable angina, stroke, TIA) within 6 months prior to enrollment
- Uncontrolled hypertension (systolic BP ≥ 150 mmHg, diastolic BP ≥ 90 mmHg)
- Active pulmonary tuberculosis, severe infections, or other uncontrolled diseases
- Active gastrointestinal perforation, fistula, or bowel obstruction.
- Inadequately controlled diabetes (fasting blood glucose \> 10 mmol/L).
- History of mental illness preventing compliance with treatment.
- Active bleeding or significant coagulation abnormalities within the last 30 days.
- Previous gastrointestinal perforation or other serious gastrointestinal conditions in the past 6 months.
- Participation in other trials that may interfere with this study.
