Proof of Mechanism Study of an Oral Hedgehog Inhibitor (GDC-0449) in Patients With Resectable Pancreatic Ductal Adenocarcinoma in the Pre-operative Window Period
- Documented tissue diagnosis of pancreatic ductal adenocarcinoma with a sufficient
amount of tissue for Laser Capture Micro-dissection (LCM) of the stromal and tumour
- Confirmed eligibility for a Whipple's or distal pancreatectomy procedure by
Multi-Disciplinary Team (MDT) and surgeon review.
- Adequate organ function defined as:
- Creatinine clearance ≥ 60ml/min (as defined by Cockroft-Goult)
- Electrolytes (Sodium (Na)/Potassium (K)/Calcium (Ca)) within institutional
- Alanine transaminase (ALT)/Aspartate transaminase (AST) <5*ULN
- Partial thromboplastin time (PTT)<2*ULN, prior supplementation with vitamin K is
- Adequate blood counts: neutrophils >1,500/μl, Hb > 6mmol/L,platelets >100.000/μl
- Albumin > 30mg/dL
- Written informed consent
- Male or female aged 18 years or over.
- World Health Organization (WHO) performance status 0-1
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests, and other study procedures.
- Males should not donate sperm during treatment or up to 3 months after the last dose.
- Women of childbearing potential are required to have a negative serum pregnancy test
(with sensitivity of at least 25 mIU/mL) within 10−14 days and within 24 hours prior
to the first dose of GDC-0449.
- Known Hepatitis B/C or Human Immunodeficiency Virus (HIV) infection
- Known hypersensitivity to GDC-0449
- Active cardiac ischemic disease (this criterion only applies for participation in the
imaging part of the study)
- Women, who are pregnant plan to become pregnant or are lactating (during the study or
for up to 12 months after the last dose).
- Concurrent participation in another clinical trial using an investigational medicinal
- Other severe acute or chronic medical or psychiatric condition, or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, or in the judgment of the investigator would make it undesirable
for the patient to enter the trial (i.e. patients is not able to swallow tablets).