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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01791985
Recruitment Status : Completed
First Posted : February 15, 2013
Last Update Posted : April 16, 2019
Sponsor:
Collaborators:
Cancer Research UK
AstraZeneca
Information provided by (Responsible Party):
Imperial College London

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
Breast Cancer Drug: AZD4547 / anastrozole or letrozole 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 2012
Actual Primary Completion Date : November 2016
Actual Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

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.





Primary Outcome Measures :
  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 [ Time Frame: 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

  2. Change in tumour size 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



Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Main Eligibility Criteria

  • Written informed consent and ability to comply with study protocol
  • Aged ≥ 25 years of age
  • Post menopausal women with histological confirmation of breast cancer with documented positive oestrogen receptor status (ER+) of primary or metastatic tumour tissue
  • ECOG performance status 0-1 and minimum life expectancy of 12 weeks
  • Fulfils criteria for previous treatment of breast cancer:
  • Safety run-in: Relapse during a single regimen of adjuvant endocrine therapy with either anastrozole or letrozole or
  • 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.
  • Prior chemotherapy in the advanced and adjuvant setting is permitted.
  • Prior treatment with exemestane with or without everolimus is permitted.

    *anastrozole or letrozole does not have to be the most recent therapy

  • 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.
  • Adequate haematological, hepatic and renal function
  • Phase IIa: Mandatory provision of tumour biopsy for assessment of oncology biomarkers
  • Safety run-in: Study entry must be preceded by a minimum of 21 days of anastrozole or letrozole treatment
  • Phase IIa: No restriction to duration of anastrozole or letrozole treatment prior to study entry.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01791985


Locations
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United Kingdom
Queen's Hospital, Burton-on-Trent
Burton-on-Trent, Staffs, United Kingdom, DE13 0RB
Russells Hall Hospital, West C8 Admin Office, 2nd Floor
Dudley, West Midlands, United Kingdom, DY1 2HQ
Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Breast Cancer Research Unit, PO Box 97, Hills Road,
Cambridge, United Kingdom, CB2 0QQ
Greater Glasgow Health Board, Beatson West of Scotland Cancer Centre, 1053 Great Western Road,
Glasgow, United Kingdom, G12 0YN
Imperial College Healthcare NHS Trust, Charing Cross Hospital,1st Floor, Department of Medical Oncology, Fulham Palace Road
London, United Kingdom, W6 8RF
The Christie NHS Foundation Trust, Wilmslow Road, Withington
Manchester, United Kingdom, M20 4BX
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
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
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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
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Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT01791985    
Other Study ID Numbers: C/23/2011
2011-000454-32 ( EudraCT Number )
First Posted: February 15, 2013    Key Record Dates
Last Update Posted: April 16, 2019
Last Verified: April 2019
Keywords provided by Imperial College London:
Breast Cancer
AZD4547
Safety Run-In
FGFR1
ER positive breast cancer
Single arm phase IIa study
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Anastrozole
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal