AZD4547 & Anastrozole or Letrozole (NSAIs) in ER+ Breast Cancer Patients Who Have Progressed on NSAIs (RADICAL)

Phase 1

Completed

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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Single arm study	AZD4547 / anastrozole or letrozole	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.

Primary Outcome Measures

Name	Time	Method
Proportion of Tumour Size Change at 12 Weeks (or Progression if Prior to Week 12)	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)	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 Outcome Measures

Name	Time	Method
Progression Free Survival	42 months	Progression Free Survival (PFS) was defined as the time from study enrolment to first evidence of progression. Progression is defined as overall progressive disease identified at follow-up or confirmed disease progression at the end of the trial or death.
Proportion of Tumour Size Change at 6, 20 and 28 Weeks	6, 20 and 28 weeks	Proportion of tumour size change at 6, 20 and 28 weeks to assess the efficacy of AZD4547 in combination with anastrozole or letrozole. This outcome measure is based on local review.
Tumour Response (RECIST Criteria) at 6, 12, 20 and 28 Weeks	6, 12, 20 and 28 weeks	Tumour response (RECIST criteria) at 6, 12, 20 and 28 weeks to assess the efficacy of AZD4547 in combination with anastrozole or letrozole. This outcome measure is based on local review.
Objective Response at 6, 12, 20 and 28 Weeks	6, 12, 20 and 28 weeks	Objective Response at 6, 12, 20 and 28 weeks to assess the efficacy of AZD4547 in combination with anastrozole or letrozole. The Objective Response Rate (ORR) is defined as the proportion of overall complete response (CR) and overall partial response (PR) among all patients who receive at least one dose of study treatment. This outcome measure is based on local review.

Locations (7): Queen's Hospital, Burton-on-Trent
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Burton-on-Trent, Staffs, United Kingdom
Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Breast Cancer Research Unit, PO Box 97, Hills Road,
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Cambridge, United Kingdom
Greater Glasgow Health Board, Beatson West of Scotland Cancer Centre, 1053 Great Western Road,
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Glasgow, United Kingdom
Russells Hall Hospital, West C8 Admin Office, 2nd Floor
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Dudley, West Midlands, United Kingdom
The Newcastle upon Tyne Hospitals NHS Foundation Trust, Sir Bobby Robson Cancer Trials Research Centre, Freeman Hospital, High Heaton
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Newcastle upon Tyne, United Kingdom
The Christie NHS Foundation Trust, Wilmslow Road, Withington
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Manchester, United Kingdom
Imperial College Healthcare NHS Trust, Charing Cross Hospital,1st Floor, Department of Medical Oncology, Fulham Palace Road
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London, United Kingdom