Fulvestrant +/- Vandetanib in Advanced Aromatase Inhibitor Resistant Breast Cancer

NCT02530411 | Unknown Phase 2 DMC

• 2 other identifiers: 2014/VCC/00132014-001208-23
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 5

Brief Summary

A randomised double blind placebo controlled phase II study of fulvestrant with or without the addition of vandetanib as treatment for patients with metastatic breast cancer resistant to aromatase inhibitor therapy.

Conditions

Neoplasms

Keywords

Hormone resistance; vandetanib; fulvestrant

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Time to event based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. - Time from randomisation to any disease progression and/or death.

  Time to event. This outcome will be assessed over an estimated period of up to 45 months.

Secondary Outcomes (6)

• Objective Response Rate

  Time to event. This outcome will be assessed when all participants have completed a minimum 12 months follow-up and at least 98 disease progression events are observed, i.e. over an estimated period of up to 45 months.

• Overall Survival

  Time to event. This outcome will be assessed over an estimated period of up to 45 months.

• Exploratory analysis: The influence of RET signalling pathway components expression on vandetanib activity.

  Data will be analysed when archival tumour tissue samples have been collected from all consenting patients. This outcome will be assessed and data presented up to 45 months.

• Safety and tolerability of the fulvestrant/vandetanib trial drug regime measured by the number of participants with reported serious adverse events (composite outcome measure).

  Initial safety reviews will be conducted after 20 and 40 patients have completed at least one cycle of treatment (estimated 8 and 16 months after enrolment of the first patient respectively). Final assessment/data presentation by 2018 (up to 45 months).

• Feasibility of use of the combined vandetanib/fulvestrant trial drug regime measured by the number of participants requiring dose delays, reductions and/or study withdrawal to manage reported serious adverse events.

  Initial safety reviews will be conducted after 20 and 40 patients have completed at least one cycle of treatment (estimated 8 and 16 months after enrolment of the first patient respectively). Final assessment/data presentation by 2018 (up to 45 months).

Study Arms (2)

Experimental

EXPERIMENTAL

Fulvestrant 500mg Intra Muscular (IM) Day 1 (D1), D15, then D1 of every 28 day cycle Vandetanib 300 mg Per os (po) daily Clinician review D1, D15, weeks 4, 8, 12, 16, 20, 24 then 12 weekly. Computerised Axial Tomography (CT) at week 8, 16, 24 then 12 weekly.

Drug: Fulvestrant; Drug: Vandetanib

Control

PLACEBO COMPARATOR

Fulvestrant 500mg IM D1, D15, then D1 of every 28 day cycle Placebo po daily Clinician review D1, D15, weeks 4, 8, 12, 16, 20, 24 then 12 weekly. CT at week 8, 16, 24 then 12 weekly.

Drug: Fulvestrant

Interventions

Fulvestrant DRUG

The pharmacology and mode of action studies established that fulvestrant is the first agent in a new class of anti-estrogens that down-regulate the estrogen receptor (ER), and can therefore be described as an ER down-regulator.

Also known as: FASLODEX™ (also previously known as ZD9238)

Control; Experimental

Vandetanib DRUG

Vandetanib is a potent inhibitor of the tyrosine kinase activity of vascular endothelial growth factor receptor (VEGFR; also known as kinase insert domain containing receptor)-2, an endothelial cell receptor for vascular endothelial growth factor (VEGF), and also possesses activity against epidermal growth factor receptor (EGFR) and Rearranged during Transfection (RET) tyrosine kinases.

Also known as: CAPRELSA™ (also previously known as ZACTIMA™, ZD6474)

Experimental

Eligibility Criteria

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

You may qualify if:

• Female ≥ 18 years
• Post-menopausal
• Minimum life expectancy 12 weeks
• Histological confirmation of ER+ve breast cancer on primary tumour at diagnosis/on biopsy of metastasis
• Histological confirmation of HER2 negative breast cancer on primary tumour at diagnosis/on biopsy of a metastasis
• Clinical or histological confirmation of metastatic or locally advanced disease not amenable to curative surgical resection
• ECOG 0-2 with no deterioration over previous 2 weeks
• Measurable or non-measurable disease
• Adequate bone marrow and organ function
• Progressive disease whilst receiving third generation aromatase inhibitor for locally advanced or metastatic BC or relapsed with metastatic disease whilst receiving third generation AI in adjuvant setting
• Radiological or objective clinical evidence of recurrence or progression on or after last systemic therapy prior to enrolment
• ≤3 prior lines of endocrine therapy for ABC
• ≤ 1 line of cytotoxic chemotherapy for ABC
• Suitable for further endocrine therapy
• Availability of archival tumour sample or fresh biopsy

You may not qualify if:

• Previous treatment with fulvestrant or inhibitors of RET pathway
• Last dose chemotherapy, immunotherapy targeted therapy, biological therapy or tumour embolisation \<21 days (\<6 weeks for nitrosurea or mitomycin C) prior to study treatment
• Last dose of palliative radiotherapy \<7 days prior to study treatment
• Rapidly progressive visceral disease not suitable for further endocrine therapy
• Spinal cord compression or brain/meningeal metastases unless asymptomatic, treated and stable and not requiring steroids for ≥ 4 weeks study treatment
• Any of the following cardiac criteria: Significant cardiac event, superior vena cava syndrome, NYHA classification of heart disease ≥2 within 12 weeks before randomisation, or presence of cardiac disease that increases risk of ventricular arrhythmia; History of arrhythmia which is symptomatic or requires treatment, symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia; Congenital long QT syndrome; History of QT prolongation associated with other medications that required discontinuation of that medication; QTcB \>480msec on screening ECG
• Electrolyte values: Potassium \<4.0 mmol/L despite supplementation, or above CTCAE Grade 1 upper limit, at randomisation; Magnesium below the normal range despite supplementation, or above CTCAE Grade 1 upper limit, at randomisation; Calcium (ionised or serum) below the normal range despite supplementation, or above Grade 1 upper limit, at randomisation
• Creatinine clearance \<30 ml/min. Patients with creatinine clearance \<50 mL/min will start at a permanently reduced vandetanib dose of 200 mg.
• Major surgery (excluding placement of vascular access) within 4 weeks before study treatment
• Evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and HIV
• With the exception of alopecia, any unresolved toxicities from previous therapy greater than CTCAE grade 1 before study treatment
• Elevated ALP in absence of bone metastasis
• History of hypersensitivity to active or inactive excipients of vandetanib or fulvestrant
• Evidence of dementia, altered mental status or any psychiatric condition that would prohibit understanding or rendering of informed consent
• Participation in another study with investigational product during last 30 days

Sponsors & Collaborators

• Velindre NHS Trust: lead
• Cancer Research UK: collaborator
• AstraZeneca: collaborator

Study Sites (5)

Royal Bournemouth Hospital

Bournemouth, Dorset, BH7 7DW, United Kingdom

RECRUITING

Royal Devon and Exeter Hospital

Exeter, England, EX2 5DW, United Kingdom

RECRUITING

Royal Cornwall Hospital

Truro, Cornwall, England, TR1 3LJ, United Kingdom

RECRUITING

Velindre Cancer Center, Velindre Hospital

Cardiff, Wales, CF14 2TL, United Kingdom

RECRUITING

Royal United Hospital Bath

Bath, BA1 3NG, United Kingdom

RECRUITING

Related Publications (1)

• Beresford M, Casbard A, Hudson Z, Carucci M, Ingarfield K, Gee J, Smith J, Kitson T, Alchami F, Madden TA, Hayward L, Hwang D, Spensley S, Waters S, Wheatley D, Jones RH. Fulvestrant plus vandetanib versus placebo for the treatment of patients with metastatic breast cancer resistant to aromatase inhibitor therapy (FURVA): a multicentre, Phase 2, randomised controlled trial. BJC Rep. 2023 Sep 14;1(1):13. doi: 10.1038/s44276-023-00016-8.

  PMID: 39516358 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

Fulvestrant; vandetanib

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Mark Beresford, MD MRCP FRCR

  Royal United Hospital NHS Trust, Bath, UK

  STUDY DIRECTOR

• Robert Jones, MD PhD MCRCP

  Velindre NHS Trust, Cardiff, UK

  STUDY DIRECTOR

Central Study Contacts

Joanna Smith, BSc MSc PhD

CONTACT

029 20687500; sealjd@cardiff.ac.uk

Tracie Madden, PhD

CONTACT

029 20687500; maddenTA1@cf.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Trial Manager

Study Record Dates

• First Submitted: March 23, 2015
• First Posted: August 21, 2015
• Study Start: April 1, 2015
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2020
• Last Updated: August 21, 2015

Record last verified: 2015-08

Locations

GB (5)