Split-course SBRT for Borderline Resectable and Locally Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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Exploratory assessment of the efficacy and safety of gemcitabine-albumin-based paclitaxel chemotherapy combined with SBRT in the treatment of newly diagnosed borderline resectable and locally advanced unresectable pancreatic cancer patients with sequential investigator selection (IC).

Detailed Description
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The question of how to administer adequate chemotherapy to synchronize SBRT treatment strategy to maximize the benefits of neoadjuvant therapy for improved prognosis of patients with borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer is a challenging and debatable issue. No studies have yet evaluated the efficacy of split-course SBRT as the neoadjuvant chemoradiotherapy regimen. The investigators aimed to study whether neoadjuvant chemotherapy plus split-course SBRT results in better outcomes in BRPC and LAPC patients.

Official Title
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Chemotherapy-based Split Stereotactic Body Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: Study Protocol of a Prospective, Single-arm Phase II Trial

Conditions
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Pancreatic Neoplasms

Intervention / Treatment
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* Drug: nab-Paclitaxel+Gemcitabine
* Radiation: split-course SBRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old and ≤ 70 years old. Histologically or cytologically confirmed adenocarcinoma of the pancreas. Borderline resectable or locally advanced pancreatic cancer proven by imaging examinations via multidisciplinary approaches according to NCCN guidelines No prior chemotherapy or radiotherapy ECOG performance status of 0 or 1. Without distant metastasis The maximum diameter of the tumor must not exceed 5 cm Acceptable hematology parameters: a. Absolute neutrophil count (ANC) ≥1500 cell/mm3 b. Platelet count ≥100,000/mm3 c. Hemoglobin (Hgb)≥9 g/dL Acceptable blood chemistry levels: a. AST/SGOT and ALT/SGPT≤2.5× upper limit of normal range (ULN) b. Total bilirubin≤1.5 ULN c. Alkaline phosphatase≤2.5× ULN d. Serum albumin>3 g/dL e. Serum creatinine≤1.5 ULN Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted. Exclusion Criteria: Age < 18 years old and > 70 years old. Prior anticancer therapy for pancreatic carcinoma. Presence of or history of metastatic pancreatic adenocarcinoma. Patients who had surgeries, chemotherapy, or other treatments before inclusion. Any other malignancy within 5 years prior to enrollment History of allergy or hypersensitivity to nab-paclitaxel or gemcitabine or any of their excipients. Peripheral sensory neuropathy Grade > 1 Serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders. Pregnant or breast feeding. Patients enrolled in other clinical trials or incompliant with regular follow-up Unwillingness or inability to comply with study procedures.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SBRT with concurrent chemotherapy<br>SBRT with nab-Paclitaxel plus Gemcitabine (nab-P+Gem) chemotherapy | Drug: nab-Paclitaxel+Gemcitabine<br>* Drug: nab-Paclitaxel 125 mg/m2 IV over approximately 30-45 min on Days 1 and 15, followed by gemcitabine 1000 mg/m2 IV infusion over approximately 30 min on Days 1 and 15 of each 28-day cycle for 6 cycles.<br>Radiation: split-course SBRT<br>* Radiation: During the first 1 and 2 cycles of chemotherapy, SBRT was given as a single irradiation of 10 Gy ⅹ 4 times (Days 2 and 16 of each 28-day cycle).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kaplan-Meier Estimate of Progression-Free Survival (PFS) | Progression-free Survival (PFS) was defined as the time from the date of the first dose to the date of disease progression or death (by any cause), whichever is earlier. The analysis day was calculated from enrollment date for one participant who was not treated. Participants who have no disease progression or have not died were censored to last tumor assessment date with progression-free. | From enrollment to 2 years after the end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kaplan-Meier Estimates for Time to Treatment Failure (TTF) | TTF was defined as the time after the first dose of study therapy to discontinuation of study therapy due to disease progression, death by any cause, or the start of a new non-protocol-defined anticancer therapy/surgery. | From enrollment to 2 years after the end of treatment | 
| Disease Control Rate (DCR) | DCR was defined as the percentage of participants with a CR or PR or SD from of date of first treatment to 16 weeks. Tumor assessments after start of non-protocol-defined anticancer therapy were excluded. | From enrollment to 2 years after the end of treatment | 
| Overall Response Rate (ORR) | ORR was defined as the percentage of participants that achieved a combined incidence of complete (CR) and partial response (PR) using RECIST 1.1 guidelines as assessed by the investigator. | From enrollment to 2 years after the end of treatment | 
| Kaplan-Meier Estimates for Overall Survival (OS) | Overall survival was defined as the time from the date of first dose of study therapy to the date of death (by any cause). | From enrollment to 2 years after the end of treatment | 
| Participants With Treatment Emergent Adverse Events (TEAEs) | TEAEs are defined as any adverse event (AE) that begin or worsen on or after the start of study drug or procedure of the study period through the maximum duration of the period plus 28 days. | From enrollment to 2 years after the end of treatment |