Conditions: Breast Cancer
Keywords: Breast Cancer AZD4547 Safety Run-In FGFR1 ER positive breast cancer Single arm phase IIa study
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 52
Healthy volunteers: no

Brief summary:
This study is looking at a new drug called AZD4547 which is being tested for the treatment of oestrogen receptor positive breast cancer. AZD4547 is a drug which specifically "blocks" proteins called fibroblast growth factor receptors (FGFR1) that are involved in the processes that help cancer cells to grow. These proteins may also be responsible for the development of resistance to hormonal therapies used to treat some breast cancers. AZD4547 is not yet approved for use in breast cancer and is therefore being used in this study as a research drug.

The investigators will also test the theory that it is not necessary for high levels of FGFR1 to be present in the body to see benefit from AZD4547. (Stage 1 only)

Detailed description:
The study will be carried out in two stages. Stage 1 is to find a suitable dose of AZD4547 which can be used together with a class of drugs called nonsteroidal aromatase inhibitors (e.g. anastrozole or letrozole) i.e. a dose which does not cause too many unacceptable side effects.

Patients with hormone sensitive (oestrogen receptor positive) breast cancer, whose current treatment with anastrozole or letrozole has recently stopped working properly will be eligible for this stage.

Stage 2 will then assess the efficacy of AZD4547, based on the change in tumour size at 12 weeks (or progression if prior to week 12), when used in combination with either anastrozole or letrozole in patients with hormone sensitive (oestrogen receptor positive) breast cancer, who have progressed on treatment with either anastrozole or letrozole in any setting.

In both stages, the study will look at how well the new treatment is tolerated.

Each patient is only allowed to take part in either stage 1 or 2.

The study will be run in 9 Hospitals across England and Scotland.

Arms:
arm 1: NSAI (anastrozole (1mg) or letrozole (2.5mg)), orally, once daily but together with twice daily AZD4547 (80mg).

AZD4547 will be given on an intermittent schedule of one week on / one week off.

Interventions: intervention 1: AZD4547 / anastrozole or letrozole
Intervention descriptions: intervention 1: Patients will continue or restart the NSAI which they have progressed\* on: either anastrozole (1mg) or letrozole (2.5mg), orally, once daily but together with twice daily AZD4547 (80mg).

AZD4547 will be given on an intermittent schedule of one week on / one week off.

\*Prior to study entry, patients must have taken anastrozole or letrozole at some stage in their treatment to date for breast cancer; and shown evidence of resistance to this therapy. The NSAI does not have to be the most recent line of treatment.

Protocol document: