Low-dose Radiotherapy Plus Chemotherapy With Gem-based Doublets and Stereotactic Radiotherapy for Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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Aim of this study is to evaluate if low-dose radiotherapy (LDR) can intensify local effect of a chemotherapy regimen with Gem-based doublets administered sequentially with stereotactic body radiotherapy (SBRT) and to assess the safety and efficacy of this combined treatment on patients affected by locally advanced pancreatic adenocarcinoma (LAPC).

Official Title
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Low-dose Radiotherapy as a Chemo-potentiator of a Induction Chemotherapy Regimen With Gem-based Doublets and Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Radiation: LDR
* Drug: Gem-based doublets
* Radiation: SBRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed adenocarcinoma of the pancreas Patients with unresectable disease based on institutional standardized criteria of unresectability or patients whose disease appeared potentially resectable on axial CT imaging but were found unresectable at surgery Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. Age ≥ 18 Patients with biliary or gastroduodenal obstruction must have drainage or surgical bypass prior to starting treatment Patients with radiographically assessable disease Adequate bone marrow, hepatic and renal function: -Hemoglobin >10.0 g/dL, absolute neutrophil count > 1.5 x 10^9/L, platelet count > 100 x 10^9/L. -Aspartate transaminase (AST or SGOT) and alanine transaminase (ALT or SGPT) should be ≤ 3 x upper limit of normal (ULN). -Total bilirubin < 2 mg/dL. Patients with elevated bilirubin due to obstruction should be stented and their bilirubin should decrease to < 2 mg/dL prior to study entry. - Creatinine < 3 mg/dL or Creatinine clearance > 40 mL/min (calculated according to Cockroft and Gault) Exclusion Criteria: Evidence of metastatic disease in the major viscera or peritoneal seeding or ascites Gastric or duodenal obstruction Previous peripheral neuropathy Previous irradiation to the planned field; previous chemotherapy for pancreatic cancer Malignancy (within the past two years) except non-melanomatous skin cancer or carcinoma in situ of the cervix, uterus, or bladder

Ages Eligible for Study
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Minimum Age: 18 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: Gem-based doublets with LDR & sequential SBRT<br>Four Gem-based doublets cycles will be administered concurrent with LDR. If no progression, three fractions of SBRT will be administered. | Radiation: LDR<br>* LDR will be delivered during each cycle of Gem-based doublets<br>* Other names: Low dose radiotherapy;Drug: Gem-based doublets<br>* 4 cycles of Gem-based doublets<br>Radiation: SBRT<br>* SBRT will be administered after the fourth Gem-based doblet cycle, if no progression; three fractions will be administered<br>* Other names: Steretactic body radiotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | defined as the time from the initiation of therapy to the time of first event (local, regional or distant progression or death due to any cause). Patients without any such event at the time of data analysis will be censored at the last date they were known to be event-free. Patients with no tumor assessments after baseline will be censored at day 1 | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity(scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events (v4.0)) | Acute gastrointestinal toxicity is defined as adverse events occurring <3 months after SBRT; long-term toxicity was defined as those occurring after 3 months. Toxicity is scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events (v4.0) | every 3 months, up to 1 year | 
| Overall survival | defined as the time from the date of initiation of therapy to date of death due to any cause. Patients who is alive on the date of last follow-up were censored on that date | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally advanced pancreatic cancer, Stereotactic Body Radiotherapy, Chemopotentiator, Low dose radiotherapy, Hyper-Radiosensitivity