AZD4547 & Anastrozole or Letrozole (NSAIs) in ER+ Breast Cancer Patients Who Have Progressed on NSAIs (RADICAL)
Study Details
Study Description
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)
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: AZD4547 / anastrozole or letrozole
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.
|
Outcome Measures
Primary Outcome Measures
- 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 assessment window - days 1 to 28 of cycle 1]
This is the primary outcome measure in the Safety Run-In part of the study
- Change in tumour size 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
Eligibility Criteria
Criteria
Main Eligibility Criteria
-
Written informed consent and ability to comply with study protocol
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Aged ≥ 25 years of age
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Post menopausal women with histological confirmation of breast cancer with documented positive oestrogen receptor status (ER+) of primary or metastatic tumour tissue
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ECOG performance status 0-1 and minimum life expectancy of 12 weeks
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Fulfils criteria for previous treatment of breast cancer:
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Safety run-in: Relapse during a single regimen of adjuvant endocrine therapy with either anastrozole or letrozole or
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Progression during first line endocrine therapy with anastrozole or letrozole for advanced breast cancer Phase IIa: Progressing or progression at some point during breast cancer treatment on endocrine therapy with a non-steroidal AI* Co-administration of a targeted agent with the non-steroidal AI is permitted providing all toxicities have recovered to CTCAE Grade 1 or below.
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Prior chemotherapy in the advanced and adjuvant setting is permitted.
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Prior treatment with exemestane with or without everolimus is permitted.
*anastrozole or letrozole does not have to be the most recent therapy
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Safety run-in: At least 1 lesion (measurable/non measurable) that can be accurately assessed by CT/MRI/plain x-ray at baseline and follow-up Phase IIa: At least 1 measurable lesion ≥ 10mm in longest diameter (or ≥ 15mm in the short axis for nodal disease) at baseline that can be accurately assessed by CT/MRI at baseline and follow up. Patients with bone only metastatic cancer must have a lytic or mixed lytic-blastic lesion that can be accurately assessed by CT or MRI.
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Adequate haematological, hepatic and renal function
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Phase IIa: Mandatory provision of tumour biopsy for assessment of oncology biomarkers
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Safety run-in: Study entry must be preceded by a minimum of 21 days of anastrozole or letrozole treatment
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Phase IIa: No restriction to duration of anastrozole or letrozole treatment prior to study entry.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Queen's Hospital, Burton-on-Trent | Burton-on-Trent | Staffs | United Kingdom | DE13 0RB |
| 2 | Russells Hall Hospital, West C8 Admin Office, 2nd Floor | Dudley | West Midlands | United Kingdom | DY1 2HQ |
| 3 | Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Breast Cancer Research Unit, PO Box 97, Hills Road, | Cambridge | United Kingdom | CB2 0QQ | |
| 4 | Greater Glasgow Health Board, Beatson West of Scotland Cancer Centre, 1053 Great Western Road, | Glasgow | United Kingdom | G12 0YN | |
| 5 | Imperial College Healthcare NHS Trust, Charing Cross Hospital,1st Floor, Department of Medical Oncology, Fulham Palace Road | London | United Kingdom | W6 8RF | |
| 6 | The Christie NHS Foundation Trust, Wilmslow Road, Withington | Manchester | United Kingdom | M20 4BX | |
| 7 | The Newcastle upon Tyne Hospitals NHS Foundation Trust, Sir Bobby Robson Cancer Trials Research Centre, Freeman Hospital, High Heaton | Newcastle upon Tyne | United Kingdom | NE7 7DN | |
| 8 | Poole Hospital NHS Foundation Trust, Top Floor, Linac Office, | Poole | United Kingdom | BH15 2JB |
Sponsors and Collaborators
- Imperial College London
- Cancer Research UK
- AstraZeneca
Investigators
- Principal Investigator: Michael Seckl, Imperial College Healthcare NHS Trust
- Principal Investigator: Nicola Cresti, Newcastle-upon-Tyne Hospitals NHS Trust
- Principal Investigator: Richard Baird, Cambridge University Hospitals NHS Foundation Trust
- Principal Investigator: Iain MacPherson, NHS Greater Glasgow and Clyde
- Principal Investigator: Amitabha Chakrabarti, Poole Hospital NHS Foundation Trust
- Principal Investigator: Mojca Persic, Burton Hospitals NHS Foundation Trust
- Principal Investigator: Anne Armstrong, The Christie NHS Foundation Trust
- Principal Investigator: Rozenn Allerton, The Dudley Group NHS Foundation Trust
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- C/23/2011
- 2011-000454-32