Proof of mechanism study of an oral Hedgehog Inhibitor (GDC-0449) in patients with resectable pancreatic ductal adenocarcinoma in the pre-operative window period
| ISRCTN | ISRCTN13491559 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13491559 |
| EudraCT/CTIS number | 2010-018776-24 |
| ClinicalTrials.gov number | NCT01096732 |
| Secondary identifying numbers | 9531 |
- Submission date
- 14/03/2011
- Registration date
- 14/03/2011
- Last edited
- 22/06/2015
- Recruitment status
- Stopped
- Overall study status
- Stopped
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English Summary
Contact information
Ms Lisa Bax
Scientific
Scientific
Cambridge Cancer Trials Centre
Box 279
Hills Road
Cambridge
CB2 0QQ
United Kingdom
| lisa.bax@addenbrookes.nhs.uk |
Study information
| Study design | Non-randomised, Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| 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 |
| 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(s) | Cambridgeshire 1 REC, 21/10/2010, ref: 10/H0304/76 |
| 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 |
| Primary outcome measure | 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 study start date | 14/02/2011 |
| Overall study end date | 31/05/2012 |
| Reason abandoned (if study stopped) | Participant recruitment issue |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 20; UK Sample Size: 20 |
| 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 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
- England
- United Kingdom
Study participating centre
Cambridge Cancer Trials Centre
Cambridge
CB2 0QQ
United Kingdom
CB2 0QQ
United Kingdom
Sponsor information
Cambridge University Hospitals NHS Foundation Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom
"ROR" |
https://ror.org/04v54gj93 |
|---|
Funders
Funder type
Government
Cambridge University Hospitals NHS Foundation Trust (UK)
No information available
Roche Products Ltd (UK)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
