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Estrogen Receptor Positive Breast CancerPhase 1/2FAKTIONNCT01992952

Fulvestrant +/- Akt Inhibition in Advanced Aromatase Inhibitor Resistant Breast Cancer

A Phase 1/2 study testing AZD5363 and Fulvestrant in people with Estrogen Receptor Positive Breast Cancer, run by Velindre NHS Trust at 21 sites in United Kingdom.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a two stage study, with an initial dose escalation phase I study and subsequent double blind randomised phase II controlled trial. Eligible patients are post-menopausal women with metastatic ER+ breast cancer not suitable for surgical resection. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Estrogen Receptor Positive Breast Cancer
What is being tested?
AZD5363 and Fulvestrant
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
149 participants
Where
21 sitesUnited Kingdom
Study dates
7 May 2014to 31 Dec 2025
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Post-menopausal Women
  • Life expectancy 3 months
  • Histological confirmation of ER+ breast cancer
  • Clinical or histological confirmation of metastatic or locally advanced disease not amenable to surgical resection
  • Measurable or non-measurable disease
  • Adequate bone marrow, renal and hepatic function
Show all 14Show fewer
  • Eastern Cooperative Oncology Group (ECOG) performance status < or equal to 2
  • Progressive disease whilst receiving an aromatase inhibitor (AI) for metastatic breast cancer (MBC)
  • Relapsed with metastatic disease whilst receiving an AI in adjuvant setting
  • Up to 3 prior lines of endocrine therapy for Advanced Breast Cancer
  • Up to 1 line of chemotherapy for Advanced Breast Cancer
  • Patient willing to donate archival tumour sample
  • Patient willing to donate baseline blood sample
  • Suitable for further endocrine therapy

Who cannot join

  • Previous treatment with fulvestrant or PI3K/mTOR(mammalian target of rapamycin )/Akt inhibitor therapy
  • Treatment with chemotherapy, immunotherapy or targeted, biologic or tumour embolisation within 21 days of study drug administration
  • Palliative radiotherapy within 7 days of study drug
  • Clinically significant abnormalities in glucose metabolism
  • Rapidly progressive visceral disease not suitable for further endocrine therapy
  • Known brain or leptomeningeal metastases
  • Any co-existing medical condition precluding trial entry including significant cardiac disease (to be defined in the protocol)
  • Concomitant medication unsuitable for combination with trial medication

Trial locations and contacts

21 sites in 1 country.

21 sites in 1 country

United Kingdom21 sites
  • Ysbyty Gwynedd

    Bangor

  • Clatterbridge Cancer Centre

    Bebington

  • Royal Blackburn Hospital

    Blackburn

  • Blackpool Victoria Hospital

    Blackpool

  • Velindre NHS Trust

    Cardiff, Cardiff

  • University Hospital of North Durham

    Durham

  • Great Western General Hospital

    Edinburgh

  • Calderdale and Huddersfield NHS Foundation Trust

    Huddersfield

  • The Ipswich Hospital NHS Trust

    Ipswich

  • University Hospitals Morecambe Bay

    Lancaster

  • St James's University Hospital

    Leeds

  • Mount Vernon Cancer Centre

    London

  • Royal Free Hospital

    London

  • Christie Hospital

    Manchester, Greater Manchester

  • Derriford Hospital

    Plymouth

  • Royal Preston Hospital

    Preston

  • Glan Clwyd Hospital

    Rhyl

  • Queen's Hospital

    Romford

  • Southampton General Hospital

    Southampton

  • Royal Stoke University Hospital

    Stoke-on-Trent

  • Royal Albert and Edward Infirmary -Wrightington

    Wigan

Other trials in United Kingdom

About this study

Official title: A Phase 1b/2 Randomised Placebo Controlled Trial of Fulvestrant +/- AZD5363 in Postmenopausal Women With Advanced Breast Cancer Previously Treated With a Third Generation Aromatase Inhibitor

This is a two stage study, with an initial dose escalation phase I study and subsequent double blind randomised phase II controlled trial. Eligible patients are post-menopausal women with metastatic ER+ breast cancer not suitable for surgical resection. Patients should be suitable for endocrine treatment, but have received no more than 3 previous lines of endocrine treatment and up to 1 line of chemotherapy for metastatic disease. They will also have had progressive disease during treatment with an aromatase inhibitor. Following the dose-escalation in stage 1, patients will be randomised to receive fulvestrant plus either placebo or 480mg (or maximum tolerated dose) of AZD5363 oral capsules or tablets taken once daily.

Patients will receive fulvestrant in combination with either placebo or AZD5363 until disease progression. Patients may continue to receive fulvestrant and AZD5363/placebo treatment even after the last trial visit.

Read the detailed description

Phase 1 (n=9-12)

As fulvestrant and AZD5363 have not previously been administered to this population, we have incorporated an initial phase I dose escalation:

  • 3 patients will receive fulvestrant 500mg on day 1 and 400mg AZD5363 oral capsules or tablets bd 4 days on and 3 days off. They will be assessed for dose limiting toxicity (DLT) on day 1, 15 and 28 of cycle 1. The safety review committee (SRC) will meet to review DLT reports when the third patient finishes cycle 1.
  • If 400mg is tolerable (0/3-6 or 1-6 has a DLT) then the dose of AZD5363 will be escalated to 480mg.
  • If 480mg is tolerable in a cohort of 6 patients then 480mg will be the Maximum tolerated dose (MTD).
  • If 480mg is not tolerable (2/6 patients have a DLT), then the 400mg dose will be the MTD.
  • If 400mg is not tolerable (2 or more patients have a DLT) then the dose will be reduced to 320mg for the next cohort of 6 patients.
  • if 320mg is tolerable in a cohort of 6 patients, then 320mg will be the MTD.
  • if 320mg is not tolerable, then the trial will not proceed. If patients are withdrawn for reasons other than toxicity during Stage 1 before DLT assessments then they will be replaced.

Phase 2 (n=136)

Recruitment in to Phase 2 will commence after all 6 patients in Stage 1 have completed at least 1 cycle of therapy and the SRC have given the go-ahead. Patients will be randomised to one of two arms:

Arm A (control arm): Fulvestrant + placebo The control arm will consist continuous 28 day cycles of fulvestrant 500mg on day 1, plus placebo capsule or tablet bd 4 days on and 3 days off.

Arm B (experimental arm): Fulvestrant + AZD5363 The experimental arm will consist continuous 28 day cycles of fulvestrant 500mg on day 1, plus AZD5363 capsule or tablet bd 4 days on and 3 days off.

A further safety assessment will be made after 20 patients have been randomised to receive AZD5363 or placebo and have at least 1 cycle of protocol treatment in stage 2.

Phase 2 will have 3 stages, this is because we want to investigate whether tumours with certain characteristics are more likely to respond to the AZD5363. As mentioned above, we will test the tumour tissue for the presence of a PIK3CA mutation (a gene encoding catalytic subunit of class 1 PI3K) and for low levels of phosphatase and tensin homolog (PTEN). Laboratory research has shown that tumours with these characteristics may respond better to the AZD5363. Tumours which do not have these characteristics are called wild-type, and we want to make sure we don't recruit too many of these patients if they might not benefit from the treatment.

We will start off by recruiting all eligible patients. However, when we know that we have 40 patients with wild-type tumours, and they have been on trial treatment for eight weeks, we will stop recruiting patients with wild-type tumours. This means that we will do a blood test to confirm the tumour has the PIK3CA mutation before a patient can be entered onto the study.

We will perform a review of the tumour measurements in this wild-type group to determine whether the tumours of the patients receiving AZD5363 have shrunk more than patients receiving placebo. If there is no evidence that the tumour has shrunk in the AZD5363 group compared to placebo, we will not recruit any more patients with wild-type tumours. If there is evidence that that the tumours have shrunk in the AZD5363 group, we will start recruiting patients with wild-type tumours again.

Being tested
AZD5363, Placebo, Fulvestrant

What participants receive

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

  • AZD5363Drug

    Up to 480mg oral tablets twice a day, taken four days on, 3 days off treatment.

  • PlaceboDrug

    Placebo tablets taken twice a day, 4 days on treatment, 3 days off treatment

  • FulvestrantDrug

    2 x 250mg injections, received on Days 1 and 15 of cycle 1, and on day 1 of each subsequent 28 day cycle.

Study groups in NCT01992952
Study groupRoleWhat they receive
AZD5363 plus fulvestrantExperimentalFulvestrant 500mg and AZD5363 4 days on 3 days off at dose determined in safety run in (maximum 480mg and minimum 320mg bd)
Receives: Drug: AZD5363; Drug: Fulvestrant
Placebo plus fulvestrantActive comparatorFulvestrant 500mg D1, D15 (cycle 1) and D1 of a 28 cycle thereafter. AZD5363 placebo 4 days on 3 days off
Receives: Drug: Placebo; Drug: Fulvestrant

What is being measured

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

  1. Phase 1b primary outcome measure: Maximum Tolerated Dose of AZD5363 in combination with fulvestrant

    To establish the MTD of AZD5363 in combination with fulvestrant and to establish a recommended phase 2 dose

    Measured: 6 months

  2. Phase 2 primary outcome: Progression free survival (PFS)

    To establish the anti-tumour activity of the combination of AZD5363 with fulvestrant as measured by progression-free survival (PFS). This is the time from enrolment to any disease progression and/or any death, defined according to strict Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 criteria. Lesions will be compared to baseline measurements to assess progression.

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months after the last patient is randomised

Secondary outcomes (6)
  1. Number of patients with adverse events

    To determine the number of patients reporting adverse events and to summarise the different types of adverse events experienced in each trial arm.

    Measured: Up to 12 months after the last patient is randomised

  2. Objective response rate

    The objective response rate will be used to determine the proportion of patients who responded to treatment.

    Measured: Up to 12 months after the last patient is randomised

  3. Overall survival

    The time from randomisation to death, with those still alive censored at date last seen

    Measured: Up to 12 months after the last patient is randomised

  4. The influence of mutational status of PIK3CA and the presence of complete loss of PTEN on outcome in the two treatment groups

    The mutational status of PIK3CA and the presence of complete loss of PTEN will be assessed at baseline.

    Measured: Up to 12 months after the last patient is randomised

  5. Fulvestrant pharmacokinetics

    The minimum concentration (Cmin) of fulvestrant will be measured to determine whether AZD5363 affects the metabolism of fulvestrant.

    Measured: Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 3 Day 1

  6. Number of patients requiring dose modifications

    The number of participants requiring dose modifications of AZD5363 and fulvestrant will be summarised for each trial arm. This will be broken down into the number of patients who withdraw from treatment and the number who were dose reduced while on treatment.

    Measured: Up to 12 months after the last patient is randomised

Timeline

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

  1. First posted25 Nov 2013 (estimated)
  2. Study start7 May 2014
  3. Primary completionMar 2019
  4. Study completion31 Dec 2025 (estimated)

Resources

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
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
149 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01992952
Sponsor's protocol ID
FAKTION
Acronym
FAKTION
Status last verified
Nov 2025
First submitted
21 Oct 2013
Last updated
26 Nov 2025
Results posted
No
Data monitoring committee
Yes

Publications

  • Howell SJ, Casbard A, Carucci M, Ingarfield K, Butler R, Morgan S, Meissner M, Bale C, Bezecny P, Moon S, Twelves C, Venkitaraman R, Waters S, de Bruin EC, Schiavon G, Foxley A, Jones RH. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial. Lancet Oncol. 2022 Jul;23(7):851-864. doi: 10.1016/S1470-2045(22)00284-4. Epub 2022 Jun 4.

    PubMed 35671774
  • Jones RH, Casbard A, Carucci M, Cox C, Butler R, Alchami F, Madden TA, Bale C, Bezecny P, Joffe J, Moon S, Twelves C, Venkitaraman R, Waters S, Foxley A, Howell SJ. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2020 Mar;21(3):345-357. doi: 10.1016/S1470-2045(19)30817-4. Epub 2020 Feb 5.

    PubMed 32035020

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AZD5363 and Fulvestrant in people with Estrogen Receptor Positive Breast Cancer, run by Velindre NHS Trust at 21 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 14 inclusion and 8 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: under way, not looking for participants, as of the sponsor's last update on 26 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 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?

This study is still under way. Results are not available in the source record yet.

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?

Phase 1b primary outcome measure: Maximum Tolerated Dose of AZD5363 in combination with fulvestrant (time frame: 6 months). 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 NCT01992952, which also lists 2 linked publications.

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 26 Nov 2025.

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