Hedgehog Inhibition for Pancreatic Ductal Adenocarcinoma (PDAC) in the Preoperative Setting (HIPPoS)

This clinical trial is looking at the effect of a new drug called GDC-0449 in patients with cancer of the pancreas. Laboratory studies have shown that this drug blocks a process in pancreatic cells thought to be involved in cancer development and spread. This process is called the ‘Hedgehog signalling pathway’. As yet, it is unclear whether blocking hedgehog signalling will directly affect the tumour cells themselves or the surrounding normal tissue. Understanding this distinction will help improve treatment strategies for pancreatic cancer. Patients will be offered to participate in this research study if they have localised pancreatic cancer that can be removed by surgery. In the period between diagnosis and surgery the investigators do not normally treat patients, however in this trial the investigators will ask patients to take GDC-0449 during the approximately two weeks until the day of surgery. All patients that enter this study will have undergone a diagnostic biopsy of the pancreatic tumour and the investigators will collect a second sample of the tumour at surgery. The main question of this study is whether the investigators can detect a change in hedgehog signalling in the normal tumour surrounding tissue. Furthermore the investigators will look very carefully whether this treatment is safe for patients. All problems before and after surgery will be carefully documented and the investigators have defined strict rules to stop the study if the investigators observe serious problems.

本临床试验旨在评估名为GDC-0449的新型药物在胰腺癌症患者中的应用效果。实验室研究表明，该药物可阻断胰腺细胞内的一类被认为与癌症发生及转移相关的过程，即Hedgehog信号通路（Hedgehog signalling pathway）。目前尚不清楚阻断该信号通路是否会直接作用于肿瘤细胞本身，或是肿瘤周围的正常组织。明确这一作用差异将有助于优化胰腺癌的治疗策略。若患者患有可通过手术切除的局限性胰腺癌，则可受邀参与本研究。通常在确诊至手术的间隔期内，研究者不会对患者进行常规治疗，但在本试验中，研究者将要求患者在确诊后至手术前的约两周内服用GDC-0449。所有入组患者均需已完成胰腺肿瘤的诊断性活检，且研究者将在手术过程中采集第二份肿瘤样本。本研究的核心问题为：研究者能否检测到肿瘤周围正常组织内Hedgehog信号通路的变化。此外，研究者还将全面评估该治疗方案对患者的安全性。研究人员将详细记录患者手术前后的所有不良事件，并已制定严格的研究终止规则，若观察到严重不良事件，将立即终止本研究。