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

Velindre NHS Trust0 sites165 target enrollmentNovember 11, 2015

ConditionsMetastatic breast cancer Cancer

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Metastatic breast cancer
Sponsor: Velindre NHS Trust
Enrollment: 165
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

2023 Results article in https://doi.org/10.1038/s44276-023-00016-8 (added 28/02/2024)

Registry

who.int

Start Date

November 11, 2015

End Date

December 31, 2021

Last Updated

2 years ago

Study Type

Interventional

Sex

Female

Investigators

Sponsor

Velindre NHS Trust

Eligibility Criteria

Inclusion Criteria

•1\. Adult female patients aged 18 years or over
•2\. Post\-menopausal patients. Post\-menopausal can be defined as either of the following criteria:
•2\.1\. Amenorrhoeic throughout AND after therapy with a third generation AI, without a GnRH analogue (eg. goserelin) AND screening FSH and estradiol in institutional post\-menopausal ranges
•2\.2\. Treatment of early or metastatic breast cancer with a third generation AI and GnRH analogue, with discontinuation of the GnRH analogue for at least 6 months AND no resumption of menstruation AND screening FSH and estradiol in institutional postmenopausal ranges
•3\. Minimum life expectancy of 12 weeks
•4\. Histological confirmation of ER\+ve breast cancer on primary tumour at diagnosis or on biopsy of a metastasis. ER is considered positive if \=10% of tumour cells stain positive for ER (whatever the intensity of staining). If no percentage score is available then a Quick (Allred) Score of \=4/8 will be considered ER positive
•5\. Histological confirmation of HER2 negative breast cancer on primary tumour at diagnosis or on biopsy of a metastasis. HER2 is considered negative by IHC if scored 0 or 1\+ by Herceptest or similar assay. If HER2 is scored 2\+ or 2\+/3\+ by IHC then HER2 gene amplification must be assessed by FISH/CISH/DDISH and the ratio of HER2 to EP17 probes must be \<2\.0
•6\. Clinical or histological confirmation of metastatic or locally advanced disease not amenable to curative surgical resection
•7\. ECOG performance status 0 to 2 with no deterioration over the previous 2 weeks
•8\. Measurable or non\-measurable disease

Exclusion Criteria

•1\. Previous treatment with fulvestrant or inhibitors of the RET pathway
•2\. Last dose chemotherapy, immunotherapy targeted therapy, biological therapy or tumour embolisation less than 21days (less than 6 weeks for nitrosurea or mitomycin C) prior to the first dose of study treatment. Note: endocrine (hormone) therapy is not considered a targeted or biological therapy for the purposes of this study. Denosumab and bisphosphonate treatment are accepted concomitant medications as long as they are started at least 14 days prior to study drug commencement.
•3\. Last dose of palliative radiotherapy less than 7 days prior to the first dose of study treatment
•4\. Rapidly progressive visceral disease not suitable for further endocrine therapy
•5\. Spinal cord compression or brain/meningeal metastases unless asymptomatic, treated and stable and not requiring steroids for at least 4 weeks before starting study treatment
•6\. Any of the following cardiac criteria:
•6\.1\. Significant cardiac event (e.g., myocardial infarction), superior vena cava syndrome, New York Heart Association (NYHA) classification of heart disease \=2 within 12 weeks before randomisation (see Appendix 2\), or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia
•6\.2\. History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE v 4\.03 Grade 3\), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Patients with atrial fibrillation controlled by medication are permitted.
•6\.3\. Congenital long QT syndrome
•6\.4\. History of QT prolongation associated with other medications that required discontinuation of that medication