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

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
• •* 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