Condition category
Cancer
Date applied
14/03/2011
Date assigned
14/03/2011
Last edited
22/06/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Stopped
Recruitment status
Stopped

Contact information

Type

Scientific

Primary contact

Ms Lisa Bax

ORCID ID

Contact details

Cambridge Cancer Trials Centre
Box 279
Hills Road
Cambridge
CB2 0QQ
United Kingdom
-
lisa.bax@addenbrookes.nhs.uk

Additional identifiers

EudraCT number

2010-018776-24

ClinicalTrials.gov number

NCT01096732

Protocol/serial number

9531

Study information

Scientific 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: a non randomised study

Acronym

HIPPoS

Study hypothesis

This clinical trial is looking at the effect of a new drug called GDC0449 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 we do not normally treat patients, however in this trial we will ask patients to take GDC0449 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 we will collect a second sample of the tumour at surgery. The main question of this study is whether we can detect a change in hedgehog signalling in the tumour tissue.

Furthermore we will look very carefully whether this treatment is safe for patients. All problems before and after surgery will be carefully documented and we have defined strict rules to stop the study if we observe serious problems.

Ethics approval

Cambridgeshire 1 REC, 21/10/2010, ref: 10/H0304/76

Study design

Non-randomised, Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Topic: National Cancer Research Network; Subtopic: Upper Gastro-Intestinal Cancer; Disease: Pancreas

Intervention

Adverse Event Monitoring: Blood sampling, Maximum of 212ml; Concomitant Medications, electrocardiogram (ECG), endoscopic ultrasound (EUS) and contrast / elastography; Physical Exam, Urinalysis, Study Entry : Registration only

Updated 22/06/2015: The study was stopped early due to poor recruitment.

Intervention type

Other

Phase

Phase II

Drug names

Primary outcome measures

Effect on stromal cell and tumour; Timepoint(s): To study the effect of GDC0449 treatment on the stromal cell and tumour cell hedgehog signalling

Secondary outcome measures

Safety & Tolerability; Timepoint(s): To study the safety and tolerability of preoperative GDC0449 treatment in patients

Overall trial start date

14/02/2011

Overall trial end date

31/05/2012

Reason abandoned

Participant recruitment issue

Eligibility

Participant inclusion criteria

1. 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
2. Confirmed eligibility for Whipple's or distal pancreatectomy procedure by Multi-Disciplinary Team (MDT) and surgeon review.
3. Adequate organ function defined as:
3.1. Creatinine clearance = 60ml/min (as defined by Cockroft-Goult)
3.2. Electrolytes (Na/K/Ca) within institutional normal limits
3.3. Alanine aminotranferease (ALT)/aspartate aminotransferase(AST) < 5*ULN
3.4. Prothrombin time test (PTT) < 2*ULN, prior supplementation with vitamin K is allowed
3.5. Adequate blood counts: neutrophils >1,500/µl, Hb > 6 mmol/L, platelets >100.000/µl
3.6. Albumin > 30mg/dL
4. Written informed consent
5. Male or female aged 18 years or over
6. WHO performance status 0-1
7. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures
8. Males should not donate sperm during treatment or up to 3 months after the last dose
9. 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 20; UK Sample Size: 20

Participant exclusion criteria

1. Known Hepatitis B/C or HIV infection
2. Known hypersensitivity to GDC-0449
3. Active cardiac ischemic disease (this criterion only applies for participation in the imaging part of the study)
4. Women who are pregnant, plan to become pregnant or are lactating (during the study or for up to 12 months after the last dose)
5. Concurrent participation in another clinical trial using an investigational medicinal product
6. 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)

Recruitment start date

14/02/2011

Recruitment end date

31/05/2012

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Cambridge Cancer Trials Centre
Cambridge
CB2 0QQ
United Kingdom

Sponsor information

Organisation

Cambridge University Hospitals NHS Foundation Trust (UK)

Sponsor details

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Sponsor type

Government

Website

Funders

Funder type

Government

Funder name

Cambridge University Hospitals NHS Foundation Trust (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Roche Products Ltd (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes