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PhaeochromocytomaPhase 1VIBRaNTNCT01941849

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

A Phase 1 study testing Vandetanib and 131I-mIBG in people with Phaeochromocytoma and Paraganglioma, run by University College, London at 3 sites in United Kingdom.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Phaeochromocytoma, Paraganglioma
What is being tested?
Vandetanib and 131I-mIBG
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
3 sitesUnited Kingdom
Study dates
Oct 2014to Dec 2015
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • Positive 123I-mIBG diagnostic scan
  • Stable blood pressure (<140/90mmHg), if appropriate, on anti-hypertensive therapy
  • No previous systemic chemotherapy within 3 months prior to registration
  • No previous mIBG therapy within 12 months prior to registration (previous cumulative activity must not exceed 15 GBq)
  • Measurable disease (RECIST v1.1)
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  • WHO performance status 0 or 1
  • Age ≥ 18
  • Estimated life expectancy > 3 months.
  • 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
  • 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
  • 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
  • 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)
  • Able to swallow oral medication
  • Capable of giving written informed consent

Who cannot join

  • Patients undergoing current treatment with curative intent
  • Previous or current malignancies of other histological types within the last 5 years (exceptions listed in the trial protocol)
  • Any prior exposure to VEGF, EGFR or RET inhibitors or history of hypersensitivity to vandetanib or any excipient agents
  • 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
  • Evidence of active uncontrolled infection (patients on antibiotics are eligible)
  • Chronic gastrointestinal disease (e.g. Inflammatory Bowel Disease) or significant bowel resection that would preclude adequate absorption
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  • 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
  • Any psychiatric or other disorder likely to impact on informed consent or ability to manage isolation
  • Major surgery within 28 days prior to registration
  • 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

Trial locations and contacts

3 sites in 1 country.

United Kingdom3 sites

  • Guy's and St Thomas' NHS Foundation Trust

    London

  • The Christie NHS Foundation Trust

    London

  • University College London Hospitals NHS Foundation Trust

    London

Other trials in United Kingdom

About this study

Official title: A Phase I Trial of Vandetanib Combined With 131I-mIBG Radiotherapy in Patients With Neuroendocrine Tumours, Advanced Phaeochromocytoma and Paraganglioma

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.

Read the detailed description

VIBRaNT is a registered phase I trial in patients with locally advanced or metastatic phaeochromocytoma or paraganglioma, not amenable to surgical resection.

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.

Being tested
Vandetanib, 131I-mIBG
Keywords
Phaeochromocytoma, Paraganglioma, Neuroendocrine Tumour, Vandetanib, 131I-mIBG, Radionucleotide Therapy, Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor Receptor (EGFR), RET, Tyrosine Kinase
Medical subject headings
Pheochromocytoma, Paraganglioma, Neuroendocrine Tumors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VandetanibDrug

    Also called Caprelsa

    100 mg, 200 mg or 300 mg taken once a day during each 12-weekly cycle

  • 131I-mIBGRadiation

    Also called Iodine-131 labelled Meta-iodobenzylguanine

    Activity will be prescribed to deliver whole body absorbed dose of 0.5 Gy (+/-10%)

Study groups in NCT01941849
Study groupRoleWhat they receive
Vandetanib + 131I-mIBGExperimentalVandetanib (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.
Receives: Drug: Vandetanib; Radiation: 131I-mIBG

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Occurrence of Dose Limiting Toxicity

    Detailed adverse event monitoring will be conducted according to CTCAE v4.03. Dose Limiting Toxicity (DLT) is defined as any adverse event or laboratory abnormality detailed in the trial protocol, that is considered to be highly probable or probable trial treatment related and commencing anytime during the DLT evaluation period (from start of cycle 1 to cycle 1 week 12). Adverse Events include: Haematological, Clinical Chemistry, Cardiovascular, Gastrointestinal, Skin.

    Measured: From start of cycle 1 to end of cycle 1 (each cycle = 12 weeks)

Secondary outcomes (3)

  1. Objective response

    Response will be assessed according to RECIST v1.1. Confirmation of complete or partial response is not required. Stable disease will be considered the best response only is a second assessment has been carried out which confirmed stable disease at least 4 weeks after trial entry. Assessment will be determined using CT scans and 123I-mIBG scans performed at baseline, then every 3 months after start of treatment until disease progression (up to 3 years from registration)

    Measured: Determined using imaging scans performed at baseline (registration), then every 3 months after start of treatment until disease progression up to 3 years from date of registration

  2. Occurrence and Severity of Adverse Events

    Will include all grade 1-5 adverse events.

    Measured: From date of registration until 30 days after completion of trial treatment (vandetanib and/or 131I-mIBG)

  3. Progression Free Survival

    Progression-free survival will be calculated from the date of trial entry to the date of documented disease progression, or death from any cause. Where progression is suspected and subsequently confirmed by scans, the date of documented suspected progression will be used.

    Measured: From date of registration to date of documented disease progression or death from any cause, whichever comes first, assessed up to 3 years from date of registration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Sep 2013 (estimated)
  2. Study startOct 2014
  3. Primary completionDec 2015
  4. Study completionDec 2015

Why it stopped: Poor patient accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01941849
Sponsor's protocol ID
UCL/12/0499
Acronym
VIBRaNT
Status last verified
Dec 2015
First submitted
10 Sep 2013
Last updated
21 Dec 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vandetanib and 131I-mIBG in people with Phaeochromocytoma and Paraganglioma, run by University College, London at 3 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 21 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Occurrence of Dose Limiting Toxicity (time frame: From start of cycle 1 to end of cycle 1 (each cycle = 12 weeks)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01941849.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2015.

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