NCT02530411

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

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

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 160 (estimated)
• Sponsor: Velindre NHS Trust · Other Government
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

For patients with advanced breast cancer that has spread around the body, hormone therapy is often the best treatment. As well as being very effective, this means that patients do not experience the toxicity and inconvenience of chemotherapy. However, eventually the cancer is likely to become resistant to hormone therapy and in this situation, although other hormone drugs can be used, they sometimes do not work very well. So it is important to find ways of getting the cancer to respond to hormone treatment again. There are many different ways in which breast cancer cells become resistant to hormone treatments, including a 'signalling' pathway in the cells called RET \[Receptor tyrosine kinase RET\] REarranged during Transfection. Research has shown increased activity of RET signalling pathways in hormone resistant cancer cells. Vandetanib is an oral drug that inhibits RET signalling in cells and has been shown in laboratory studies to prevent the growth of breast cancer cells which have become resistant to hormone therapy. Hormone therapy drugs include tamoxifen, and the aromatase inhibitors (anastrozole, letrozole and exemestane). The investigators therefore believe that giving vandetanib together with hormone therapy may help prevent resistance to treatment in patients with breast cancer. In this trial the investigators will combine this drug with fulvestrant, another hormone therapy drug which is sometimes used alone in patients who have developed resistance to aromatase inhibitors, or tamoxifen. So patients entering the trial will have one drug, fulvestrant, which is known to work and may also be given the experimental drug, vandetanib. To properly determine if vandetanib works as the investigators believe, this study will compare the activity of vandetanib combined with fulvestrant with fulvestrant combined with an inactive, 'placebo' tablet in a group of patients for whom treatment with single agent fulvestrant is thought appropriate. The investigators plan to recruit a total of 160 patients. Half of them will be given fulvestrant and vandetanib and half will be given fulvestrant and placebo, and the treatment a particular patient will get will be chosen by random chance. Neither the patient nor the patients doctor will know whether the patient is getting vandetanib or the inactive placebo. The most important measure of effect will be the time until the cancer grows again, but the study will also look closely at the side effects of the drugs. The investigators will also look at whether the way in which an individual responds relates to the results from laboratory studies on the RET pathways carried out on previously stored tumour samples. This will mean that patients will not need to have additional biopsy samples taken.

Conditions

• Neoplasms

Interventions

Type	Name	Description
DRUG	Fulvestrant	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.
DRUG	Vandetanib	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.

Timeline

• Start date: 2015-04-01
• Primary completion: 2018-12-01
• Completion: 2020-12-01
• First posted: 2015-08-21
• Last updated: 2015-08-21

Locations

5 sites across 1 country: United Kingdom