A Single Arm Phase IIa Study (With Combination SRI) to Assess the Safety & Efficacy of AZD4547 in Combination With Either Anastrozole or Letrozole in ER+ Breast Cancer Patients Who Have Progressed on Treatment With Anastrozole or Letrozole
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Imperial College London
- Enrollment
- 52
- Locations
- 7
- Primary Endpoint
- Proportion of Tumour Size Change at 12 Weeks (or Progression if Prior to Week 12)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 25 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Single arm study
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.
Intervention: AZD4547 / anastrozole or letrozole (Drug)
Outcomes
Primary Outcomes
Proportion of Tumour Size Change at 12 Weeks (or Progression if Prior to Week 12)
Time Frame: 12 weeks
This is the primary outcome measure in the Randomised Phase IIa part of the study. This is the proportion of tumour size change from baseline to week 12 (or progression if prior to week 12) based on local review of results.
Number of Participants With Serious Adverse Events (SAEs)
Time Frame: Dose limiting toxicity (DLT) assessment window - days 1 to 28 of cycle 1
Safety and tolerability of AZD4547 to be used in combination with a standard dose of anastrozole or letrozole, as assessed by Dose limiting toxicity (DLT) This is the primary outcome measure in the Safety Run-In part of the study.
Secondary Outcomes
- Progression Free Survival(42 months)
- Proportion of Tumour Size Change at 6, 20 and 28 Weeks(6, 20 and 28 weeks)
- Tumour Response (RECIST Criteria) at 6, 12, 20 and 28 Weeks(6, 12, 20 and 28 weeks)
- Objective Response at 6, 12, 20 and 28 Weeks(6, 12, 20 and 28 weeks)