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

This study has been terminated.
(Slow recruitment)
Sponsor:
Collaborators:
Roche Pharma AG
Genentech
Information provided by (Responsible Party):
Lisa Bax, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01096732
First received: March 30, 2010
Last updated: January 7, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Pancreatic Ductal Adenocarcinoma
Drug: GDC-0449
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Cambridge University Hospitals NHS Foundation Trust:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 3
Study Start Date: February 2011
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GDC-0449
Study drug.
Drug: GDC-0449
Gelatine capsules of 150mg.Taken O.D. for 14 days.
Other Name: VISMODEGIB

Detailed Description:

Please contact Principal Investigators team for full details.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01096732

Locations
United Kingdom
Cambridge University Hospitals NHS Foundation Trust
Cambridge, United Kingdom, CB2 0QQ
Sponsors and Collaborators
Lisa Bax
Roche Pharma AG
Genentech
Investigators
Principal Investigator: David Tuveson, MD PhD Cancer Research UK
  More Information

No publications provided

Responsible Party: Lisa Bax, Trial Coordinator, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01096732     History of Changes
Other Study ID Numbers: OCRD 201014
Study First Received: March 30, 2010
Last Updated: January 7, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Cambridge University Hospitals NHS Foundation Trust:
Pancreatic
adenocarcinoma
cancer

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma, Ductal, Breast
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Ductal
Neoplasms, Ductal, Lobular, and Medullary
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on July 29, 2014