Hedgehog Inhibition For Pancreatic Ductal Adenocarcinoma (PDAC) In The Preoperative Setting (HIPPoS)

Study Overview

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.

Please contact Principal Investigators team for full details.

Pancreatic Ductal Adenocarcinoma

DRUG: GDC-0449

OCRD 201014

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2010-03-30	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2014-01-07
First Submitted that Met QC Criteria 2010-03-30	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2014-01-08
First Posted (ESTIMATED) 2010-03-31	Results First Posted N/A	Last Verified 2014-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: GDC-0449 Study drug.	DRUG: GDC-0449 Gelatine capsules of 150mg.Taken O.D. for 14 days.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: GDC-0449

Study drug.

DRUG: GDC-0449

Gelatine capsules of 150mg.Taken O.D. for 14 days.

Primary Outcome Measures	Measure Description	Time Frame
To study the effect of GDC-0449 treatment on the stromal cell and tumour cell hedgehog signalling in patients with Pancreatic Ductal Adenocarcinoma.	1. To study the effect of GDC-0449 treatment on the stromal cell and tumour cell hedgehog signalling in patients with Pancreatic Ductal Adenocarcinoma. 2. To study the safety and tolerability of pre-operative GDC-0449 treatment in patients who undergo Whipple's or distal pancreatectomy surgery for Pancreatic Ductal Adenocarcinoma.	18 months

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Roche Pharma AG
Genentech, Inc.

Investigators

PRINCIPAL_INVESTIGATOR: David Tuveson, MD PhD, Cancer Research UK

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

PatientS

Caregivers

Clinical Trial Record