Preoperative, Proton- Radiotherapy Combined With Chemotherapy for Borderline Resectable Pancreatic Cancer

Обзор

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.

Подробное описание

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.

Вмешательства

• Лучевая терапия Proton Ions
  According to the radiation plan (between 50.4 and a maximum of 60.2 Gy) after Chemotherapy with Nab-PACLitaxel (Abraxane®) + Gemcitabine and concomitant to Capecitabine.
• Препарат Nab-PACLitaxel
  Chemotherapy will be delivered upfront for three cycles (week 2-4, week 6-8 and week 10-12) with combined Nab-PACLitaxel (Abraxane®) and Gemcitabine Therapy. It will be administered as intra venous infusion over 30 minutes.
• Препарат Gemcitabine
  Chemotherapy will be delivered upfront for three cycles (week 2-4, week 6-8 and week 10-12) with combined Nab-PACLitaxel (Abraxane®) and Gemcitabine Therapy. Gemcitabine will also be administered as intra venous infusion over 30 minutes immediately after Nab-PACLitaxel.
• Препарат Capecitabine
  Concomitant to proton-radiotherapy (on the same days, within week 14-19)
• Процедура Surgical resection of the pancreas (when feasible)
  Pre surgical re-evaluation will be performed at week 21 after enrollment. Patients fulfilling surgery-entry criteria, which consist of no distant metastasis, no massive ascites, no massive pleural effusion, no serious infection, no serious, unresolved chemoradiotherapy related, adverse events and adequate organ system function, will undergo surgery on week 22 (± 1 week). This should be performed via laparotomy.

Первичные конечные точки

• Toxicity - Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [Срок оценки: from enrollment to six months after surgery]
• Perioperative Mortality and Complications [Срок оценки: 90 days postoperatively]

Вторичные конечные точки (9)

• Toxicity - CTCAE v5.0 [Срок оценки: from enrollment to six months after surgery]
• Tumor recurrence [Срок оценки: 260 weeks after therapy]
• Progression free survival [Срок оценки: 260 weeks after therapy]
• Overall survival [Срок оценки: 282 weeks]
• Pathologic tumor response [Срок оценки: 260 weeks]
• Radiologic response [Срок оценки: 263 weeks after proton therapy]
• Quality of Life questionnaire: Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep) [Срок оценки: 282 weeks]
• Quality of Life questionnaire: European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-30) [Срок оценки: 282 weeks]
• Quality of Life questionnaire: Brief Pain Inventory [Срок оценки: 282 weeks]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Другое

Центры проведения

Австрия · 2 центра

• EBG MedAustron GmbH — Wiener Neustadt
• Department of Surgery, LK Wiener Neustadt — Wiener Neustadt

Идентификаторы

NCT: NCT04894643 · PARC-MA-062019

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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