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.