Breast CancerPhase 1/2RADICALNCT01791985

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

A Phase 1/2 study testing AZD4547 / anastrozole or letrozole in people with Breast Cancer, run by Imperial College London at 7 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 25 years and older, women only
Conditions the study is for: Breast Cancer
What is being tested?: AZD4547 / anastrozole or letrozole
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 52 participants
Where: 7 sitesUnited Kingdom
Study dates: Jul 2012to Dec 2018
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 25 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

None listed.

Who cannot join

Treatment with any of the following:
Safety run-in: more than 1 regimen of endocrine therapy for advanced breast cancer
previous exposure to any FGFR inhibitor
Safety run in: more than 1 prior regimen of chemotherapy for advanced breast cancer.
potent inhibitors or inducers of CYP3A4 or CYP2D6, or substrates of CYP3A4 within 2 weeks prior to first dose of study treatment (3 weeks for St John's Wort)
major surgery within 4 weeks prior to first dose of study treatment

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radiotherapy with a wide field of radiation within 4 weeks prior to first dose of study treatment; or radiotherapy with a limited field of radiation for palliation within 2 weeks before the first dose of study treatment
With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at time of starting study
Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment
Any evidence of severe or uncontrolled systemic diseases or active infection
Any of the following cardiac criteria:
Resting corrected QT interval (QTc) >470 ms
Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval
Inadequate bone marrow reserve or organ function as defined by any one of the following parameters:
Haemoglobin < 9.0 g/dL (<90.0 g/L) Absolute neutrophil count (ANC) < 1.5 x 109 /L Platelet count < 100 x 109 /L Alanine aminotransferase > 2.5 x Upper Limit of Normal (ULN) if no demonstrable liver metastases or > 5 x ULN in the presence of liver metastases Aspartate aminotransferase > 2.5 x ULN if no demonstrable liver metastases or > 5 x ULN in the presence of liver metastases Total bilirubin > 1.5 x ULN if no demonstrable liver metastases or > 3 x ULN in the presence of liver metastases Creatinine > 1.5 times ULN or creatinine clearance <50ml/min Corrected calcium > ULN Phosphate > ULN
Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated Investigational Medicinal Product (IMP) or previous significant bowel resection that would preclude absorption of AZD4547 or anastrozole or letrozole
History of hypersensitivity to anastrozole or letrozole
History of another malignancy within 5 yrs prior to starting study treatment, except adequately treated basal or squamous cell carcinoma of the skin, carcinoma of the cervix and the disease under study
Any of the following ophthalmological criteria:*
Current evidence or previous history of retinal pigmented epithelium detachment (RPED)
Previous laser treatment or intra-ocular injection for treatment of macular degeneration
Current evidence or previous history of soft drusen, drusenoid RPE detachment and wet macular degeneration.
Current evidence or previous history of retinal vein occlusion (RVO)
Current evidence or previous history of retinal degenerative diseases (e.g. hereditary) *Patients with uncontrolled glaucoma or intra-ocular pressure >21 mmHg at screening should be referred for ophthalmological management and the condition controlled prior to first dose of study treatment.
Concurrent treatment with another investigational agent or use of another investigational agent within 30 days or 5 half lives, whichever is longer, preceding the first dose of study treatment
Concurrent treatment with prohibited medications and wash out period for that drug will not have been completed before starting study medication

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

United Kingdom7 sites

Queen's Hospital, Burton-on-Trent
Burton-on-Trent, Staffs, DE13 0RB
Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Breast Cancer Research Unit, PO Box 97, Hills Road,
Cambridge, CB2 0QQ
Russells Hall Hospital, West C8 Admin Office, 2nd Floor
Dudley, West Midlands, DY1 2HQ
Greater Glasgow Health Board, Beatson West of Scotland Cancer Centre, 1053 Great Western Road,
Glasgow, G12 0YN
Imperial College Healthcare NHS Trust, Charing Cross Hospital,1st Floor, Department of Medical Oncology, Fulham Palace Road
London, W6 8RF
The Christie NHS Foundation Trust, Wilmslow Road, Withington
Manchester, M20 4BX
The Newcastle upon Tyne Hospitals NHS Foundation Trust, Sir Bobby Robson Cancer Trials Research Centre, Freeman Hospital, High Heaton
Newcastle upon Tyne, NE7 7DN

Other trials in United Kingdom

About this study

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

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)

Read the 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.

Conditions: Breast Cancer
Being tested: AZD4547 / anastrozole or letrozole
Keywords: Breast Cancer, AZD4547, Safety Run-In, FGFR1, ER positive breast cancer, Single arm phase IIa study
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AZD4547 / anastrozole or letrozoleDrug
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.

Study groups in NCT01791985
Study group	Role	What they receive
Single arm study	Experimental	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. Receives: Drug: AZD4547 / anastrozole or letrozole

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Serious Adverse Events (SAEs)
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.
Measured: Dose limiting toxicity (DLT) assessment window - days 1 to 28 of cycle 1
Proportion of Tumour Size Change at 12 Weeks (or Progression if Prior to Week 12)
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.
Measured: 12 weeks

Secondary outcomes (4)

Proportion of Tumour Size Change at 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.
Measured: 6, 20 and 28 weeks
Tumour Response (RECIST Criteria) at 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.
Measured: 6, 12, 20 and 28 weeks
Objective Response at 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.
Measured: 6, 12, 20 and 28 weeks
Progression Free Survival
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.
Measured: 42 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2012Dec 2018

First posted15 Feb 2013 (estimated)
Study startJul 2012
Primary completionNov 2016
Study completionDec 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Breast CancerStudies of the same condition, open and under way.
More trials run by Imperial College LondonThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 52 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01791985
Sponsor's protocol ID: C/23/2011
Other IDs: 2011-000454-32
Acronym: RADICAL
Status last verified: Apr 2022
First submitted: 13 Feb 2013
Last updated: 22 Aug 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Coombes RC, Badman PD, Lozano-Kuehne JP, Liu X, Macpherson IR, Zubairi I, Baird RD, Rosenfeld N, Garcia-Corbacho J, Cresti N, Plummer R, Armstrong A, Allerton R, Landers D, Nicholas H, McLellan L, Lim A, Mouliere F, Pardo OE, Ferguson V, Seckl MJ. Results of the phase IIa RADICAL trial of the FGFR inhibitor AZD4547 in endocrine resistant breast cancer. Nat Commun. 2022 Jun 10;13(1):3246. doi: 10.1038/s41467-022-30666-0.
PubMed 35688802

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 22 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01791985
Acronym / sponsor ID: RADICAL / C/23/2011
Conditions: Breast Cancer
Keywords: Breast Cancer, AZD4547, Safety Run-In, FGFR1, ER positive breast cancer, Single arm phase IIa study
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 52 participants (actual)
Lead sponsor: Imperial College LondonUniversity, hospital or other
Collaborators: Cancer Research UK, AstraZeneca
Study start: Jul 2012 (actual)
Primary completion: Nov 2016 (actual)
Study completion: Dec 2018 (actual)
First posted: 15 Feb 2013 (estimated)
Results: Posted 22 Aug 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

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

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Single arm study	Experimental	Drug: AZD4547 / anastrozole or letrozoleNSAI (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.

Who may qualify

Ages: 25 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (0 listed)

Key exclusion criteria (27 listed)

Treatment with any of the following:
With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at time of starting study
Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment
Any evidence of severe or uncontrolled systemic diseases or active infection
Any of the following cardiac criteria:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AZD4547 / anastrozole or letrozolePatients 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.	Drug	Single arm study

Primary outcome

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.
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.

4 secondary outcomes

Proportion of Tumour Size Change at 6, 20 and 28 Weeks
Time frame: 6, 20 and 28 weeks
Tumour Response (RECIST Criteria) at 6, 12, 20 and 28 Weeks
Time frame: 6, 12, 20 and 28 weeks
Objective Response at 6, 12, 20 and 28 Weeks
Time frame: 6, 12, 20 and 28 weeks
Progression Free Survival
Time frame: 42 months

Results and safety

Results posted to the registry on 22 Aug 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AZD4547	52	44

Primary outcome: Number of Participants With Serious Adverse Events (SAEs)

Time frame: Dose limiting toxicity (DLT) assessment window - days 1 to 28 of cycle 1. Count of participants. Unit: Participants

Measure	AZD4547 n = 52
Value	10

Primary outcome: Proportion of Tumour Size Change at 12 Weeks (or Progression if Prior to Week 12)

Time frame: 12 weeks. Mean (Standard Deviation). Unit: Proportion of tumour size change

Measure	AZD4547 n = 43
Value	0.08 (0.32)

AZD4547: Mean: 0.08

Population analysed: Out of 52 enrolled patients, 43 patients have analyzable data. Prior to week 12, there were 8 patients who discontinued study treatment prior to progression and 1 patient who had disease progression died before tumour measurements could be taken. Therefore a total of 9 patients cannot be included in the analysis of the primary outcome.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Events (AEs) were collected throughout the study, from the point that the RADICAL team confirmed patient eligibility until the end of patient follow-up, 42 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AZD4547	10 of 52 (19.2%)	52 of 52 (100%)	2 of 52

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35688802Coombes RC, Badman PD, Lozano-Kuehne JP, Liu X, Macpherson IR, Zubairi I, Baird RD, Rosenfeld N, Garcia-Corbacho J, Cresti N, Plummer R, Armstrong A, Allerton R, Landers D, Nicholas H, McLellan L, Lim A, Mouliere F, Pardo OE, Ferguson V, Seckl MJ. Results of the phase IIa RADICAL trial of the FGFR inhibitor AZD4547 in endocrine resistant breast cancer. Nat Commun. 2022 Jun 10;13(1):3246. doi: 10.1038/s41467-022-30666-0.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Michael Seckl principal investigator

Imperial College Healthcare NHS Trust

Nicola Cresti principal investigator

Newcastle-upon-Tyne Hospitals NHS Trust

Richard Baird principal investigator

Cambridge University Hospitals NHS Foundation Trust

7 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AZD4547 / anastrozole or letrozole in people with Breast Cancer, run by Imperial College London at 7 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Serious Adverse Events (SAEs) (time frame: Dose limiting toxicity (DLT) assessment window - days 1 to 28 of cycle 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01791985, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2022.