Preoperative, Proton- Radiotherapy Combined With Chemotherapy for Borderline Resectable Pancreatic Cancer
- Conditions
- Pancreatic CancerProton Therapy
- Interventions
- Radiation: Proton IonsProcedure: Surgical resection of the pancreas (when feasible)
- Registration Number
- NCT04894643
- Lead Sponsor
- EBG MedAustron GmbH
- Brief Summary
This is an interventional, single arm, open-label, feasibility trial with gemcitabine and nab-paclitaxel, followed by concomitant proton therapy and capecitabine, followed by re-evaluation and surgery (when feasible) for patients with borderline resectable pancreatic cancer.
- Detailed Description
This is an interventional, single arm, open label, feasibility trial of preoperative chemotherapy + concomitant chemo-proton therapy followed by surgery (when feasible) for patients with borderline resectable pancreatic cancer. Aim of this study is to test referral and enrollment procedures as well as technical feasibility. Proton therapy will be delivered in MedAustron, which is a stand alone facility. Pancreatic cancer patients are typically complex cases that require multidisciplinary care. Moreover delivery of high dose of proton therapy to large volumes including the upper abdomen lymphnodes and pancreatic neural plexus is technically challenging, therefore a feasibility study is deemed necessary. Following this study, a larger study will be performed aiming to confirm the ability of preoperative chemotherapy + concomitant chemo-proton therapy to improve resectability and ultimately outcome of borderline resectable pancreatic cancer without increase in toxicity.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 10
- Patients with histologically or cytologically confirmed diagnosis of pancreatic cancer
- Diagnosis of borderline resectable cancer according to the international consensus definition 2017.
- Negative staging for distant metastasis
- Blood test within the following limits absolute neutrophil count > 1,500 cells/mm³, platelet count > 100,000 cells/mm³, Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) < 2.5 times the upper limit of normal, total bilirubin < 2.5 times the upper limit of normal if patient had recent biliary stenting, total bilirubin < 1.5 times the upper limit of normal if no biliary stenting was done, serum creatinine within normal range (0.6-1.5 mg/dl) with a creatinine clearance > 30 ml/min (as estimated by Cockroft Gault equation)
- Age > 18 years
- Karnofsky index ≥ 70
- No tumor infiltration of stomach or duodenum
- The patient is informed of the diagnosis and is able to give informed consent (Ability of subject to understand character and individual consequences of the study protocol)
- Women of fertile age must have adequate conception prevention measures and must not breast feed
- Signed Informed Consent (must be available before study inclusion)
- Non-exocrine tumors
- Major medical or psychiatric comorbidities that contraindicate radiation therapy, chemotherapy or surgery
- Presence of distant metastasis
- Pregnancy or unwilling to do adequate conception prevention
- Lactating and unwilling to discontinue lactation
- Men of childbearing potential not willing to use effective means of contraception
- Known allergic/hypersensitivity reaction to any of the components of study treatments
- Previous diagnosis of another neoplasm with worse prognosis as compared with the one in this study
- Metallic prosthesis or other condition that prevent an adequate imaging for target volume definition
- Loco-regional conditions that contraindicate radiotherapy e.g. active infections in the area
- Previous abdominal radiotherapy
- Prior systemic treatment for pancreatic cancer
- Hypersensitivity to PACLitaxel, albumin, gemcitabine or to any of the excipients of the chemotherapy
- Severe hepatic impairment
- Baseline Neutrophil Counts < 1.5 x 10^9/L
- Baseline Grade ≥ 2 sensory or motor neuropathy
- Patient refusal
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Preoperative, proton- radiotherapy combined with chemotherapy Nab-PACLitaxel Patients treated with three cycles of chemotherapy with Nab-PACLitaxel (Abraxane®) (125 mg/m² on day 1, 8, 15; powder for making a infusion solution) and Gemcitabine (1000 mg/m² on day 1, 8, 15; powder for making a infusion solution), followed by concomitant chemotherapy with capecitabine (1.660ml/m² on 5 days per week during the radiation therapy) and proton-therapy (with simultaneous integrated boost (SIB) 50.4 Gy Relative Biological Effectiveness (RBE) and 60.2 Gy (RBE) in 28 fractions of 1.8 Gy (RBE) and 2.15 Gy (RBE) 5 days per week), followed by re-evaluation and surgery Preoperative, proton- radiotherapy combined with chemotherapy Proton Ions Patients treated with three cycles of chemotherapy with Nab-PACLitaxel (Abraxane®) (125 mg/m² on day 1, 8, 15; powder for making a infusion solution) and Gemcitabine (1000 mg/m² on day 1, 8, 15; powder for making a infusion solution), followed by concomitant chemotherapy with capecitabine (1.660ml/m² on 5 days per week during the radiation therapy) and proton-therapy (with simultaneous integrated boost (SIB) 50.4 Gy Relative Biological Effectiveness (RBE) and 60.2 Gy (RBE) in 28 fractions of 1.8 Gy (RBE) and 2.15 Gy (RBE) 5 days per week), followed by re-evaluation and surgery Preoperative, proton- radiotherapy combined with chemotherapy Surgical resection of the pancreas (when feasible) Patients treated with three cycles of chemotherapy with Nab-PACLitaxel (Abraxane®) (125 mg/m² on day 1, 8, 15; powder for making a infusion solution) and Gemcitabine (1000 mg/m² on day 1, 8, 15; powder for making a infusion solution), followed by concomitant chemotherapy with capecitabine (1.660ml/m² on 5 days per week during the radiation therapy) and proton-therapy (with simultaneous integrated boost (SIB) 50.4 Gy Relative Biological Effectiveness (RBE) and 60.2 Gy (RBE) in 28 fractions of 1.8 Gy (RBE) and 2.15 Gy (RBE) 5 days per week), followed by re-evaluation and surgery Preoperative, proton- radiotherapy combined with chemotherapy Gemcitabine Patients treated with three cycles of chemotherapy with Nab-PACLitaxel (Abraxane®) (125 mg/m² on day 1, 8, 15; powder for making a infusion solution) and Gemcitabine (1000 mg/m² on day 1, 8, 15; powder for making a infusion solution), followed by concomitant chemotherapy with capecitabine (1.660ml/m² on 5 days per week during the radiation therapy) and proton-therapy (with simultaneous integrated boost (SIB) 50.4 Gy Relative Biological Effectiveness (RBE) and 60.2 Gy (RBE) in 28 fractions of 1.8 Gy (RBE) and 2.15 Gy (RBE) 5 days per week), followed by re-evaluation and surgery Preoperative, proton- radiotherapy combined with chemotherapy Capecitabine Patients treated with three cycles of chemotherapy with Nab-PACLitaxel (Abraxane®) (125 mg/m² on day 1, 8, 15; powder for making a infusion solution) and Gemcitabine (1000 mg/m² on day 1, 8, 15; powder for making a infusion solution), followed by concomitant chemotherapy with capecitabine (1.660ml/m² on 5 days per week during the radiation therapy) and proton-therapy (with simultaneous integrated boost (SIB) 50.4 Gy Relative Biological Effectiveness (RBE) and 60.2 Gy (RBE) in 28 fractions of 1.8 Gy (RBE) and 2.15 Gy (RBE) 5 days per week), followed by re-evaluation and surgery
- Primary Outcome Measures
Name Time Method Toxicity - Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 from enrollment to six months after surgery Incidence of CTCAE version 5.0 Grade 4 non hematological toxicity from enrollment to six months after surgery
Perioperative Mortality and Complications 90 days postoperatively Incidence of 90-days-perioperative mortality and incidence of Clavien Dindo Grade III complication rate during hospitalization
- Secondary Outcome Measures
Name Time Method Tumor recurrence 260 weeks after therapy local and loco-regional (i.e. in-field) tumor recurrence
Pathologic tumor response 260 weeks Assessment of pathologic tumor response to pre-operative combined proton- chemotherapy (R0 margin and N0, degree of tumor cell necrosis in the resected tumor specimen)
Toxicity - CTCAE v5.0 from enrollment to six months after surgery CTCAE V5.0 toxicity from enrollment to six month after surgery
Quality of Life questionnaire: European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-30) 282 weeks Questionnaire developed to assess the quality of life of cancer patients. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / quality of life (QoL) represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.
Quality of Life questionnaire: Brief Pain Inventory 282 weeks The Brief Pain Inventory (BPI) is a measurement tool for assessing clinical pain.The interference items were now presented with 0-10 scales, with 0=no interference and 10=interferes completely.
Progression free survival 260 weeks after therapy loco-regional progression-free survival
Quality of Life questionnaire: Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep) 282 weeks Patient reported Quality of Life (for assessing disease-related symptoms and health-related quality of life). The higher the score the better the Quality of Life.
Overall survival 282 weeks Overall survival
Radiologic response 263 weeks after proton therapy Assessment of radiologic response of pre-operative chemoradiotherapy. Response to preoperative treatment will be scored with the Japan Pancreas Society (JPS) classification which is a synthesis from the Evans and College of American Pathologists classification (Grade 1: poor or no response to Grade 4: complete response)
Trial Locations
- Locations (2)
EBG MedAustron GmbH
🇦🇹Wiener Neustadt, Niederösterreich, Austria
Department of Surgery, LK Wiener Neustadt
🇦🇹Wiener Neustadt, Austria