Phase I Trial of Vandetanib Combined With 131I-mIBG to Treat Patients With Advanced Phaeochromocytoma and Paraganglioma

Inclusion Criteria: 1. Histopathological/cytological diagnosis of advanced phaeo/PG defined as patients with local or metastatic disease not amenable to surgical resection, or R1 resection post original surgical debulking 2. Positive 123I-mIBG diagnostic scan 3. Stable blood pressure (\<140/90mmHg), if appropriate, on anti-hypertensive therapy 4. No previous systemic chemotherapy within 3 months prior to registration 5. No previous mIBG therapy within 12 months prior to registration (previous cumulative activity must not exceed 15 GBq) 6. Measurable disease (RECIST v1.1) 7. WHO performance status 0 or 1 8. Age ≥ 18 9. Estimated life expectancy \> 3 months. 10. Adequate bone marrow function: Haemoglobin ≥ 100 g/L, White Blood Cell ≥ 3.0 x 10\^9/L, Absolute neutrophil ≥ 1.5 x 10\^9/L, Platelet ≥ 100 x 10\^9/L 11. Adequate liver function: Total bilirubin ≤1.5 x Upper Limit of Normal (ULN); ALT/AST and ALP≤ 2.5 x ULN or ≤ 5 x ULN if related to liver metastases 12. Adequate renal function: Serum urea and creatinine \< 1.5x ULN AND Calculated creatinine clearance (GFR) ≥50 mL/min. If the calculated GFR is below 50, isotope clearance test is required to confirm GFR ≥50 mL/min 13. Electrolytes: Potassium ≥ 4.0 mmol/L and ≤ 5.5 mmol/L, Magnesium ≥ Lower Limit of Normal and ≤ 1.23 mmol/L, Corrected calcium within institution normal range 14. Negative pregnancy test for women of child-bearing potential AND be using adequate barrier contraception, which must be continued for 12 months after completion of treatment (male patients must also agree to use barrier contraception during the trial and for 12 months after completion of treatment) 15. Able to swallow oral medication 16. Capable of giving written informed consent Exclusion Criteria: 1. Patients undergoing current treatment with curative intent 2. Previous or current malignancies of other histological types within the last 5 years (exceptions listed in the trial protocol) 3. Any prior exposure to VEGF, EGFR or RET inhibitors or history of hypersensitivity to vandetanib or any excipient agents 4. Evidence of severe or uncontrolled systemic diseases or laboratory finding that in the view of the investigator makes it undesirable for the patient to participate in the trial 5. Evidence of active uncontrolled infection (patients on antibiotics are eligible) 6. Chronic gastrointestinal disease (e.g. Inflammatory Bowel Disease) or significant bowel resection that would preclude adequate absorption 7. Cardiovascular exclusion criteria (complete list provided in the trial protocol): * Significant cardiac event (myocardial infarction), New York Heart Association Class II or above, within 12 weeks before registration, or presence of cardiac disease that in the opinion of the investigator increased the risk of ventricular arrhythmia * Prior or current cardiomyopathy * Baseline LVEF \< 40% as measured by ECHO/MUGA * Atrial fibrillation with heart rate \>100 bpm * Unstable ischaemic heart disease (myocardial infarction within 6 months prior to starting treatment, or angina requiring use of nitrates more than once weekly) * History of arrhythmia that was symptomatic or required treatment * QTcB prolongation \>480 ms at baseline * QT prolongation with other medications that required discontinuation of that medication 8. Any psychiatric or other disorder likely to impact on informed consent or ability to manage isolation 9. Major surgery within 28 days prior to registration 10. Brain metastases or spinal cord compression, unless treated at least four weeks before the first dose and stable without steroid treatment for 10 days 11. Any concomitant medications that may affect QTc, induce or inhibit CYP3A4 function (with the exception of somatostatin or somatostatin analogue) and/or prohibited medications 12. Women who are pregnant or lactating