Trial record 6 of 53 for:    "paraganglioma" OR "Paraganglioma"

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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified September 2013 by University College, London
Sponsor:
Collaborators:
Cancer Research UK
AstraZeneca
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01941849
First received: September 10, 2013
Last updated: NA
Last verified: September 2013
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Phaeochromocytoma
Paraganglioma
Drug: Vandetanib
Radiation: 131I-mIBG
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Vandetanib Combined With 131I-mIBG Radiotherapy in Patients With Neuroendocrine Tumours, Advanced Phaeochromocytoma and Paraganglioma

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Occurrence of Dose Limiting Toxicity [ Time Frame: From start of cycle 1 to end of cycle 1 (each cycle = 12 weeks) ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Objective response [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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)

  • Occurrence and Severity of Adverse Events [ Time Frame: From date of registration until 30 days after completion of trial treatment (vandetanib and/or 131I-mIBG) ] [ Designated as safety issue: Yes ]
    Will include all grade 1-5 adverse events.

  • Progression Free Survival [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 18
Study Start Date: January 2014
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: Vandetanib
100 mg, 200 mg or 300 mg taken once a day during each 12-weekly cycle
Other Name: Caprelsa
Radiation: 131I-mIBG
Activity will be prescribed to deliver whole body absorbed dose of 0.5 Gy (+/-10%)
Other Name: Iodine-131 labelled Meta-iodobenzylguanine

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.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 therapy for advanced or metastatic disease
  5. Measurable disease (RECIST v1.1)
  6. WHO performance status 0 or 1
  7. Age ≥ 16
  8. Estimated life expectancy > 3 months.
  9. Adequate bone marrow function: Haemoglobin ≥ 100 g/L, White Blood Cell count ≥ 3.0 x 10^9/L, Absolute neutrophil count ≥ 1.5 x 10^9/L, Platelet count ≥ 100 x 10^9/L
  10. Adequate liver function: Total bilirubin ≤1.5 x Upper Limit of Normal (ULN), ALT or AST ≤ 5 x ULN, ALP ≤ 5 x ULN
  11. Adequate renal function: Serum urea and serum creatinine < 1.5x ULN AND Calculated creatinine clearance (GFR) ≥50 mL/min estimated using a validated creatinine clearance calculation. If the calculated GFR is below 60, isotope clearance test is required to confirm GFR ≥50 mL/min
  12. Electrolytes: Potassium ≥ 4.0 mmol/L and ≤ 5.5 mmol/L, Magnesium ≥ Lower Limit of Normal (LLN) and ≤ 1.23 mmol/L, Corrected calcium within institution normal range
  13. 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)
  14. Able to swallow oral medication
  15. 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. 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
  4. Evidence of active uncontrolled infection (patients on antibiotics are eligible)
  5. Refractory nausea and vomiting, chronic gastrointestinal disease or significant bowel resection that would preclude adequate absorption
  6. Cardiovascular exclusion criteria:

    • Significant cardiac event (myocardial infarction), superior vena cava syndrome, New York Heart Association (NYHA) 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
    • Symptomatic/uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Patients with atrial fibrillation controlled by medication are permitted
    • 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
    • Congenital long QT syndrome or 2nd degree relative with unexplained sudden death under 40 years of age
    • QT prolongation with other medications that required discontinuation of that medication
  7. Any psychiatric or other disorder likely to impact on informed consent
  8. Major surgery within 28 days prior to registration
  9. Brain metastases or spinal cord compression, unless treated at least four weeks before the first dose and stable without steroid treatment for 10 days
  10. Any concomitant medications that may affect QTc, induce or inhibit CYP3A4 function (with the exception of somatostatin or somatostatin analogue) and/or prohibited medications
  11. Women who are pregnant or lactating
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01941849

Contacts
Contact: Rubina Begum 020 7679 9514 ctc.vibrant@ucl.ac.uk
Contact: Marian Duggan 020 7679 9883 ctc.vibrant@ucl.ac.uk

Locations
United Kingdom
University College London Hospitals NHS Foundation Trust Not yet recruiting
London, United Kingdom
Principal Investigator: Christina Thirlwell         
Guy's and St Thomas' NHS Foundation Trust Not yet recruiting
London, United Kingdom
Principal Investigator: Debashis Sarker         
The Christie NHS Foundation Trust Not yet recruiting
London, United Kingdom
Principal Investigator: Wasat Mansoor         
Sponsors and Collaborators
University College, London
Cancer Research UK
AstraZeneca
Investigators
Principal Investigator: Christina Thirlwell University College London (UCL) Cancer Institute
Principal Investigator: Debashis Sarker Kings College London, Guy's Hospital
  More Information

No publications provided

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01941849     History of Changes
Other Study ID Numbers: UCL/12/0499
Study First Received: September 10, 2013
Last Updated: September 10, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: National Institute for Health Research
United Kingdom: Research Ethics Committee

Keywords provided by University College, London:
Phaeochromocytoma
Paraganglioma
Neuroendocrine Tumour
Vandetanib
131I-mIBG
Radionucleotide Therapy
Vascular Endothelial Growth Factor (VEGF)
Epidermal Growth Factor Receptor (EGFR)
RET
Tyrosine Kinase

Additional relevant MeSH terms:
Paraganglioma
Pheochromocytoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
3-Iodobenzylguanidine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014