Preoperative, Proton- Radiotherapy Combined With Chemotherapy for Borderline Resectable Pancreatic Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Toxicity - Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically or cytologically confirmed diagnosis of pancreatic cancer
- •Diagnosis of borderline resectable cancer according to the international consensus definition
- •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)
排除标准
- •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
研究组 & 干预措施
Preoperative, proton- radiotherapy combined with chemotherapy
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
干预措施: Proton Ions (Radiation)
Preoperative, proton- radiotherapy combined with chemotherapy
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
干预措施: Nab-PACLitaxel (Drug)
Preoperative, proton- radiotherapy combined with chemotherapy
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
干预措施: Gemcitabine (Drug)
Preoperative, proton- radiotherapy combined with chemotherapy
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
干预措施: Capecitabine (Drug)
Preoperative, proton- radiotherapy combined with chemotherapy
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
干预措施: Surgical resection of the pancreas (when feasible) (Procedure)
结局指标
主要结局
Toxicity - Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
时间窗: 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
时间窗: 90 days postoperatively
Incidence of 90-days-perioperative mortality and incidence of Clavien Dindo Grade III complication rate during hospitalization
次要结局
- Tumor recurrence(260 weeks after therapy)
- Pathologic tumor response(260 weeks)
- Toxicity - CTCAE v5.0(from enrollment to six months after surgery)
- Quality of Life questionnaire: European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-30)(282 weeks)
- Quality of Life questionnaire: Brief Pain Inventory(282 weeks)
- Progression free survival(260 weeks after therapy)
- Quality of Life questionnaire: Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep)(282 weeks)
- Overall survival(282 weeks)
- Radiologic response(263 weeks after proton therapy)