Phase I Trial of Vandetanib Combined With 131I-mIBG to Treat Patients With Advanced Phaeochromocytoma and Paraganglioma (VIBRaNT)
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.
|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|
- 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.
- 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.
|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)|
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.
100 mg, 200 mg or 300 mg taken once a day during each 12-weekly cycle
Other Name: CaprelsaRadiation: 131I-mIBG
Activity will be prescribed to deliver whole body absorbed dose of 0.5 Gy (+/-10%)
Other Name: Iodine-131 labelled Meta-iodobenzylguanine
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01941849
|Contact: Rubina Begum||020 7679 email@example.com|
|Contact: Marian Duggan||020 7679 firstname.lastname@example.org|
|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|
|University College London Hospitals NHS Foundation Trust||Not yet recruiting|
|London, United Kingdom|
|Principal Investigator: Christina Thirlwell|
|Principal Investigator:||Christina Thirlwell||University College London (UCL) Cancer Institute|
|Principal Investigator:||Debashis Sarker||Kings College London, Guy's Hospital|