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

January 7, 2014 updated by: Lisa Bax

Proof of Mechanism Study of an Oral Hedgehog Inhibitor (GDC-0449) in Patients With Resectable Pancreatic Ductal Adenocarcinoma in the Pre-operative Window Period

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Please contact Principal Investigators team for full details.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 2

Contacts and Locations

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

Study Locations

  • United Kingdom
      • Cambridge, United Kingdom, CB2 0QQ
        • Cambridge University Hospitals NHS Foundation Trust

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.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

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.
Other Names:
  • VISMODEGIB

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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.
Time Frame: 18 months
  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

Collaborators and Investigators

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

Sponsor

Lisa Bax

Collaborators

Roche Pharma AG
Genentech, Inc.

Investigators

  • Principal Investigator: David Tuveson, MD PhD, Cancer Research UK

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 Major Dates

Study Start

February 1, 2011

Primary Completion (Actual)

August 1, 2012

Study Completion (Actual)

August 1, 2012

Study Registration Dates

First Submitted

March 30, 2010

First Submitted That Met QC Criteria

March 30, 2010

First Posted (Estimate)

March 31, 2010

Study Record Updates

Last Update Posted (Estimate)

January 8, 2014

Last Update Submitted That Met QC Criteria

January 7, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OCRD 201014

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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