Locally advanced or metastatic pancreatic cancer MedDRA version: 14.1 Level: LLT Classification code 10033600 Term: Pancreatic adenocarcinoma non-resectable System Organ Class: 100000004864
Conditions
Interventions
Product Name: Vandetanib
Product Code: ZD6474
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: vandetanib
CAS Number: 443913
Sponsors
University of Liverpool
Royal Liverpool and Broadgreen University Hospitals Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years. 2. Histologically or cytologically proven pancreatic ductal adenocarcinoma or undifferentiated carcinoma of the pancreas.* 3. Locally advanced or metastatic disease precluding curative surgical resection or definitive locally directed therapies such as chemo radiation. Patients who have relapsed following previously resected Pancreatic Cancer can be included. 4. Contrast enhanced computerised tomography (CT) scan of the thorax, abdomen and pelvis within 28 days prior to commencing treatment. 5. Unidimensionally measurable disease as shown by CT scan, in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) guidelines (version 1.1). 6. ECOG performance status 0, 1 or 2 where the investigator feels that treatment with combination chemotherapy, for example FOLFIRINOX, is not appropriate. 7. Platelets =100 x 109/l; WBC = 3 x 109/l; neutrophils = 1.5 x 109/l at entry. 8. Documented Life expectancy > 3 months. 9. Informed written consent *Patients will be approached for consenting to provide either an additional core of tissue material for biomarker discovery at the same time as diagnostic biopsy or in those patients that have already had a diagnostic biopsy to undergo a second biopsy after randomisation into the trial. Neither of these biopsies are compulsory. Patient who don't wish to have extra tissue taken for Biomarker discovery will be approached for consent to released surplus tissue from the original diagnostic specimen if this exists. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 84 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 56
Exclusion criteria
Exclusion criteria: 1. Laboratory results: • Serum bilirubin = 1.5x the upper limit of reference range (ULRR). • Haemoglobin 5.5 mmol/L • Magnesium below the normal range despite supplementation, or > 1.23 mmol/L • Serum calcium is > 2.9 mmol/L. In cases where serum calcium is below the normal range this can be substituted with the value for calcium adjusted for albumin, if this is below the normal range despite supplementation patients should be excluded. • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or alkaline phosphatase (ALP) >2.5 x ULRR or > 5x ULRR if judged by the investigator to be related to liver metastases. 2. Medical or psychiatric conditions compromising informed consent. 3. Intracerebral metastases or meningeal carcinomatosis. 4. Major surgery within 4 weeks or incompletely healed surgical incision before starting study therapy. 5. Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol. 6. Clinically significant cardiovascular event (e.g. myocardial infarction, superior vena cava syndrome (SVC), New York Heart Association (NYHA) classification of heart disease =2 within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia. 7. History of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation), which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded. 8. QTc prolongation with other medications that required discontinuation of that medication. 9. Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age. 10. Presence of left bundle branch block (LBBB). 11. QTc with Bazett’s correction that is un-measurable or = 480 msec on screening ECG. (Note: If a subject has a QTc interval = 480 msec on screening ECG, the screening ECG may be repeated up to two times and the ECGs must be at least 24 hours apart. The average QTc of the ECGs (either two or three) must be <480msec in order for the patient to be eligible. Patients who are receiving a drug that has a risk of inducing Torsades-de-Pointes (see appendix C) are excluded if QTc is = 460 msec. 12. Any concurrent medication with a known risk of inducing Torsades-de-Pointes that cannot be stopped 2 weeks prior to first dose(please see Appendix C). Any concurrent medication with a possible or conditional risk of inducing Torsades de Pointes, that in the investigator’s opinion cannot be discontinued, are allowed; however, these patients must be monitored closely (please see Appendix C). 13.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess whether overall survival time using gemcitabine plus vandetanib is longer than that using gemcitabine alone as the first treatment for advanced or metastatic pancreatic cancer.; Secondary Objective: To compare between the two treatment groups - Progression free survival (PFS) - Objective response rate (ORR) - Disease control rate - Toxicity and safety - Patient pain assessment Exploratory objectives To discover possible biomarkers to predict additional benefit of vandetanib over gemcitabine alone for subsequent validation in larger scale studies. ;Primary end point(s): Overall survival (OS) time in patients receiving gemcitabine and vandetanib therapy versus gemcitabine alone | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Comparison between the two treatment groups for: o Progression-free survival time o objective response rate o disease control rate o toxicity and safety o Patient Pain assessment • To discover possible biomarkers to predict additional benefit of vandetanib for subsequent validation in larger scale studies. | — |
Countries
United Kingdom
Outcome results
None listed