ViP is a double blinded clinical trial which will compare gemcitabine and vandetanib chemotherapy with gemcitabine alone in patients with locally advanced or metastatic pancreatic carcinoma.

Inclusion Criteria:

• Age ≥ 18 years.
• Histologically or cytologically proven pancreatic ductal adenocarcinoma or undifferentiated carcinoma of the pancreas.
• 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.
• Contrast enhanced computerised tomography (CT) scan of the thorax, abdomen and pelvis within 28 days prior to commencing treatment.
• Unidimensionally measurable disease as shown by CT scan, in accordance with RECIST guidelines (version 1.1)
• ECOG performance status 0, 1 or 2 where the investigator feels that treatment with combination chemotherapy.
• Platelets ≥100 x 109/l; WBC ≥ 3 x 109/l; neutrophils ≥ 1.5 x 109/l at entry.
• Documented Life expectancy > 3 months.
• Informed written consent

Exclusion Criteria:

• Laboratory results:

  • Serum bilirubin ≥ 1.5x the upper limit of reference range (ULRR).
  • Haemoglobin < 10G/dl
  • Creatinine clearance < 30 mL/minute (calculated by Cockcroft-Gault formula)**. Patients with a creatinine clearance of ≥30mL/minute and <50mL/minute should begin vandetanib on a reduced dose of 200mg.
  • Potassium, ≤4.0 mmol/L despite supplementation; or > 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.

• Medical or psychiatric conditions compromising informed consent.

• Intracerebral metastases or meningeal carcinomatosis.

• Major surgery within 4 weeks or incompletely healed surgical incision before starting study therapy.

• Evidence of severe or uncontrolled systemic disease or any concurrent condition

• Clinically significant cardiovascular eventclassification 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.

• History of arrhythmia which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded.

• QTc prolongation with other medications that required discontinuation of that medication.

• Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age.

• Presence of left bundle branch block (LBBB).

• QTc with Bazett's correction that is un-measurable or ≥ 480 msec on screening ECG. Patients who are receiving a drug that has a risk of inducing Torsades-de-Pointes are excluded if QTc is ≥ 460 msec.

• Any concurrent medication with a known risk of inducing Torsades-de-Pointes, that in the investigator's opinion cannot be discontinued, are allowed.

• Concomitant medications that are potent inducers.

• Hypertension not controlled by medical therapy.

• Currently active diarrhoea.

• Malabsorption syndrome.

• Pregnancy or breast feeding.

• Previous chemotherapy for locally advanced and metastatic disease. Adjuvant chemotherapy for resected pancreatic cancer will be permitted provided that chemotherapy was completed > 12 months previously.

• Radiotherapy within the last 4 weeks prior to start of study treatment.

• Concurrent malignancies or invasive cancers diagnosed within past 5 years.

• Chemotherapy directed at tumour apart from that described in this protocol.

• All men or women of reproductive potential, unless using at least two contraceptive precautions, one of which must be a condom.