Carbon Ions Radiation Therapy for Resectable or Borderline Resectable Pancreas Adenocarcinoma

Study Overview
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Brief Summary
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Relapses free survival will be evaluated as efficacy of carbon ions radiation therapy released before surgery.

Detailed Description
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Enrolled subjects will undergo to 3 cycles of Folfirinox before re-evaluation of the lesion. Then, 4D planning and imaging with respiratory gating end rescanning technique will be adopted to calculate the optimal treatment plan to carbon ions radiation therapy: 38.4 Gy[RBE] is the prescribed dose to CTV. 4.8 Gy[RBE]/fraction will be delivered 4 times a week in two weeks. 4/6 weeks after hadrontherapy, after a CT scan with contrast, patient will undergo to a surgery. After 4/6 weeks, Gemcitabine will be administered for 6 cycles. Secondary endpoints of the trial are overall survival, resectability rate (operable vs borderline operable), acute toxicity within 3 months, 3-6 months, over 6 months.

Official Title
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Phase II Clinical Study on Resectable or Borderline Resectable Pancreas Adenocarcinoma Preoperative Treatment With Chemotherapy and Carbon Ions Radiation Therapy (Hadrontherapy)

Conditions
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Cancer of Pancreas, Pancreas Adenocarcinoma, Resectable Pancreatic Cancer

Intervention / Treatment
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* Drug: Preoperative chemotherapy
* Radiation: Preoperative radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologic/cytologic diagnosis of exocrine pancreas tumour resectable or borderline resectable exocrine pancreatic tumour (according to operability criteria) no metastasis from US, CT, PET, MRI or laparotomy Karnofsky index >= 70 stomach and duodenum not infiltrated by tumour given informed consent to study procedures Hb > 9 g/dL, N> 1500, PLT> 100000 creatininemia < 1.5 mg/dL; bilirubinemia < 1.5 times upper normal values; albumin > 3 g/dL DPD normal activity contraception required and breast feeding not permitted Exclusion Criteria: non resectable, locally advanced tumours insular cells tumour comorbidities excluding abdominal surgery and/or chemo- radiation therapy known metastasis DPD low activity inability to attend study procedures and follow ups pregnancy previous diagnosis of other tumour with more disadvantageous prognosis then the study object metallic biliary stent metallic prothesis or any other condition to prevent from target volume individuation and dose calculation clinical condition preventing from radiation therapy (i.e. infections in the irradiation area) medical and/or psychical condition preventing from radiation therapy past radiation therapy on abdomen.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Interventional Model Description: The trial enrolls subjects that will receive in order: chemotherapy, carbon ion therapy, followed by surgical resection after 4/6 weeks then adjuvant chemotherapy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Preoperatory chemoradiation therapy with carbon ions<br>Chemoradiation followed by surgery | Drug: Preoperative chemotherapy<br>* Preoperative chemotherapy, carbon ion therapy, surgery<br>* Other names: Folinic acid, Irinotecan, fluorouracil, oxaliplatin;Radiation: Preoperative radiotherapy<br>* Preoperative chemotherapy, carbon ion therapy, surgery<br>* Other names: Carbon ion therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | The local progression free survival is measured | The local progression free survival will be assessed at 1-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | the overall survival of enrolled patients is considered | The overall survival of enrolled patients will be assessed at 2-years | 
| resectability rate R0 stratified (operable vs not operable) | how many surgeries completed according to the procedures and with histopathological margins free from the disease/enrolled patients | time of surgery (4-6 weeks after radiotherapy) | 
| Incidence of acute, medium term and late toxicity according to CTCAE v 4.0 grading toxicity | Incidence of acute, medium term and late toxicity according to CTCAE v 4.0 grading toxicity | The incidence of acute and medium term toxicity will be assessed up to 90 and 180 post-operative days respectively. The incidence of late toxicity will be assessed through study completion, an average of 1 year. | 
| intra and perioperatory complications | intra and perioperatory complications | The incidence of intra- and perioperatory complications will be assessed up to 30 post-operative days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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carbon ion radiation therapy, exocrine pancreas, pancreas tumour