Phase I Trial of Vandetanib Combined With 131I-mIBG to Treat Patients With Advanced Phaeochromocytoma and Paraganglioma
NCT ID: NCT01941849
Last Updated: 2015-12-21
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
WITHDRAWN
PHASE1
INTERVENTIONAL
2014-10-31
2015-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Patients will receive vandetanib (an inhibitor of VEGF, EGFR and RET tyrosine kinase) in combination with standard radiation therapy Iodine-131 labelled Meta-iodobenzylguanidine (131I-mIBG).
Vandetanib and 131I-mIBG will be given in 12-weekly cycles: 131I-miBG will be given on day 1 of each cycle and vandetanib will started on day 1 of each cycle and continue to be taken once every day. The phase I trial aims to determine with recommended phase II dose of vandetanib (either 100, 200 or 300 mg once daily) - the dose of vandetanib that patients will receive will depend on the dose under investigation at the time of patient registration.
The vandetanib dose will be determined by the Modified Continual Reassessment Method (mCRM) - a toxicity model which described the probability of a toxicity occurring at each dose level, which is based on clinical judgement and any available toxicity data.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Vandetanib + 131I-mIBG
Vandetanib (100, 200 or 300 mg once daily) in combination with 131I-mIBG radiation therapy (activity to be prescribed to deliver whole body absorbed dose of 0.5 Gy) on day 1 of each 12-weekly cycle.
Patients will receive up to 4 cycles of vandetanib in combination with 131I-mIBG.
Vandetanib
100 mg, 200 mg or 300 mg taken once a day during each 12-weekly cycle
131I-mIBG
Activity will be prescribed to deliver whole body absorbed dose of 0.5 Gy (+/-10%)
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Vandetanib
100 mg, 200 mg or 300 mg taken once a day during each 12-weekly cycle
131I-mIBG
Activity will be prescribed to deliver whole body absorbed dose of 0.5 Gy (+/-10%)
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
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
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
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Cancer Research UK
OTHER
AstraZeneca
INDUSTRY
University College, London
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Christina Thirlwell
Role: PRINCIPAL_INVESTIGATOR
University College London (UCL) Cancer Institute
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Guy's and St Thomas' NHS Foundation Trust
London, , United Kingdom
The Christie NHS Foundation Trust
London, , United Kingdom
University College London Hospitals NHS Foundation Trust
London, , United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
UCL/12/0499
Identifier Type: -
Identifier Source: org_study_id