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

NCT01941849 | Withdrawn Phase 1 DMC

• 1 other identifier: UCL/12/0499
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Phaeochromocytoma; Paraganglioma

Keywords

Phaeochromocytoma; Paraganglioma; Neuroendocrine Tumour; Vandetanib; 131I-mIBG; Radionucleotide Therapy; Vascular Endothelial Growth Factor (VEGF); Epidermal Growth Factor Receptor (EGFR); RET; Tyrosine Kinase

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (3)

• Objective response

  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

• Occurrence and Severity of Adverse Events

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

• Progression Free Survival

  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

Study Arms (1)

Vandetanib + 131I-mIBG

EXPERIMENTAL

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; Radiation: 131I-mIBG

Interventions

Vandetanib DRUG

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

Also known as: Caprelsa

Vandetanib + 131I-mIBG

131I-mIBG RADIATION

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

Also known as: Iodine-131 labelled Meta-iodobenzylguanine

Vandetanib + 131I-mIBG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University College, London: lead
• Cancer Research UK: collaborator
• AstraZeneca: collaborator

Study Sites (3)

Guy's and St Thomas' NHS Foundation Trust

London, United Kingdom

Location

The Christie NHS Foundation Trust

London, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, United Kingdom

Location

MeSH Terms

Conditions

Pheochromocytoma; Paraganglioma; Neuroendocrine Tumors

Interventions

vandetanib; 3-Iodobenzylguanidine

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Iodobenzenes; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Hydrocarbons, Iodinated; Hydrocarbons, Halogenated

Study Officials

• Christina Thirlwell

  University College London (UCL) Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2013
• First Posted: September 13, 2013
• Study Start: October 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 21, 2015

Record last verified: 2015-12

Locations

GB (3)