IORT on Borderline Resectable Pancreatic Cancer

Study Overview
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Brief Summary
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This phase II study investigates the efficacy of IORT for patients with borderline resectable pancreatic cancer. The purpose of the study is to investigate whether the addition of IORT, after FOLOFIRINOX-base chemotherapy, and SBRT, increases the 3-year survival rate. A total of 101 patients will be enrolled, and these patients will receive IORT of 10 to 20 Gy, according to the resection status (to the tumor bed after resection, or to the tumor in situ in case of non-resection).

Detailed Description
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Treatment outcomes of borderline resectable pancreatic cancer are still poor even after completion of FOLFIRINOX-based chemotherapy and radical resection. A growing body of literature is demonstrating that Stereotactic body radiation therapy (SBRT) and Intraoperative radiotherapy (IORT), within a multimodal approach, allow to obtain better oncological outcome, at the price of low to negligible rates of morbidity and mortality. The investigators hypothesize that a total neoadjuvant scenario, with the best current therapy, based on up to 6 months of FOLFIRINOX (minimum 4), SBRT and IORT (in situ or after surgery) would increase the disease-specific survival of borderline resectable pancreatic cancer patients. An historical cohort will be used as a comparison group. Considering the intention-to-treat design and the institutional rates of chemotherapy completion and exploration/resection of borderline resection pancreatic cancer patients, a total of 100 patients will be enrolled in this phase II trial. Patients submitted to IORT, will receive IORT of 10 to 20 Gy according to the resection status (to the tumor bed after resection, or to the tumor in situ in case of non-resection).

Official Title
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A Phase II Study of Primary Chemotherapy, Stereotactic Body Radiation Therapy, and Intraoperative Radiation Therapy in Borderline Resectable Pancreatic Adenocarcinoma

Conditions
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Borderline Resectable Pancreatic Cancer

Intervention / Treatment
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* Radiation: Intraoperative radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Biopsy-proven, previously untreated borderline resectable PC, defined according to the NCCN guidelines v1.2019; Age 18-80 years; Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; Adequate bone marrow function (absolute neutrophil count ≥1500 per cubic millimeter; platelet count ≥100.000 per cubic millimeter; hemoglobin level ≥10 g per deciliter), liver function (serum total bilirubin level ≤1.5 times the upper limit of the normal range), and renal function (creatinine clearance ≥50 ml per minute); Ability to understand the characteristics of the clinical trial; Written informed consent. Exclusion Criteria: • Ampullary, biliary, or duodenal adenocarcinoma; pancreatic adenocarcinoma in the background of an intraductal papillary mucinous neoplasia (IPMN), other uncommon pancreatic adenocarcinomas (acinar-cell, squamous, giant-cell osteoclastic-like); Invasive cancer in the last 5 years requiring radiation therapy to the upper abdomen or chemotherapy; Symptomatic heart failure or coronary artery disease; Pregnant or lactating women; Impaired mental state or language problems.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: IORT group<br>Intraoperative administration of 10 to 20 Gy after surgery or as an in situ treatment in case resection will not be performed | Radiation: Intraoperative radiotherapy<br>* IORT will be delivered as follows: Radical resection --> delivery of 10-15 Gy to the tumor bed Non radical resection --> delivery of 15-20 Gy to the tumor in situ<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-specific survival |  | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | 36 months | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 |  | 36 months | 
| Rate of margin-free surgery |  | 30 days | 
| Rate of surgical complications |  | Up to 90 days after surgery | 
| Resection rate |  | Intraoperative | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pancreatic cancer, Borderline resectable pancreatic cancer, Intraoperative radiotherapy (IORT), Total neoadjuvant therapy