Clinical Trial · NCT01941849

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

Overview

The phase I trial aims to determine the recommended phase II dose (RP2D) of vandetanib in combination with standard radiation therapy, 131I-mIBG, in patients with advanced phaeochromocytoma (phaeo) and paraganglioma (PG) by assessing the safety and tolerability of the combination treatment.

Sponsor

University College, London

Phase

Phase 1

Contacts

Christina Thirlwell (PRINCIPAL_INVESTIGATOR)

ClinicalTrials.gov

NCT01941849

Drug / Compound

mIBG

Isotope(s):

Target(s):

Ligand Class: Small Molecules

Eligibility

Inclusion

Measurable disease (RECIST v1.1)
Estimated life expectancy \> 3 months.
Positive 123I-mIBG diagnostic scan
Stable blood pressure (\<140/90mmHg), if appropriate, on anti-hypertensive therapy
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
Able to swallow oral medication
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
No previous mIBG therapy within 12 months prior to registration (previous cumulative activity must not exceed 15 GBq)
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)
WHO performance status 0 or 1
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
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
No previous systemic chemotherapy within 3 months prior to registration
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

Exclusion

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
Baseline LVEF \< 40% as measured by ECHO/MUGA
Unstable ischaemic heart disease (myocardial infarction within 6 months prior to starting treatment, or angina requiring use of nitrates more than once weekly)
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
Brain metastases or spinal cord compression, unless treated at least four weeks before the first dose and stable without steroid treatment for 10 days
Any concomitant medications that may affect QTc, induce or inhibit CYP3A4 function (with the exception of somatostatin or somatostatin analogue) and/or prohibited medications
Women who are pregnant or lactating
QT prolongation with other medications that required discontinuation of that medication
Major surgery within 28 days prior to registration
History of arrhythmia that was symptomatic or required treatment
Prior or current cardiomyopathy
QTcB prolongation \>480 ms at baseline
Previous or current malignancies of other histological types within the last 5 years (exceptions listed in the trial protocol)
Evidence of active uncontrolled infection (patients on antibiotics are eligible)
Cardiovascular exclusion criteria (complete list provided in the trial protocol):
Any prior exposure to VEGF, EGFR or RET inhibitors or history of hypersensitivity to vandetanib or any excipient agents
Patients undergoing current treatment with curative intent
Atrial fibrillation with heart rate \>100 bpm
Chronic gastrointestinal disease (e.g. Inflammatory Bowel Disease) or significant bowel resection that would preclude adequate absorption