Clinical trial NCT01096732: Hedgehog Inhibition for Pancreatic Ductal Adenocarcinoma (PDAC) in the Preoperative Setting (HIPPoS)
Official title: Proof of Mechanism Study of an Oral Hedgehog Inhibitor (GDC-0449) in Patients With Resectable Pancreatic Ductal Adenocarcinoma in the Pre-operative Window Period
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pancreatic Ductal Adenocarcinoma
Keywords: Pancreatic
adenocarcinoma
cancer
Lead sponsor: Cambridge University Hospitals NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
name: Genentech, Inc.
First posted: 2010-03-31
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: Please contact Principal Investigators team for full details.

Eligibility criteria: Inclusion Criteria:

* Documented tissue diagnosis of pancreatic ductal adenocarcinoma with a sufficient amount of tissue for Laser Capture Micro-dissection (LCM) of the stromal and tumour compartments.
* 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 ≥ 50ml/min (as defined by Cockcroft-Gault)
  * Electrolytes (Sodium (Na)/Potassium (K)/Calcium (Ca)) within institutional normal limits
  * Alanine transaminase (ALT)/Aspartate transaminase (AST) \<5\*ULN
  * Partial thromboplastin time (PTT)\<2\*ULN, prior supplementation with vitamin K is allowed
  * Adequate blood counts: neutrophils \>1,500/μl, Hb \> 6mmol/L,platelets \>100.000/μl
  * Albumin ≥ 25mg/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.

Exclusion Criteria:

* 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 product.
* 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).

Primary outcomes:
measure: To study the effect of GDC-0449 treatment on the stromal cell and tumour cell hedgehog signalling in patients with Pancreatic Ductal Adenocarcinoma.
timeFrame: 18 months
Secondary outcomes:
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
Study officials:
affiliation: Cancer Research UK
name: David Tuveson, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: