Metastatic Breast CancerPhase 2PAKTNCT02423603
PAKT: AZD5363 in Combination With Paclitaxel in Triple-Negative Advanced or Metastatic Breast Cancer
A Phase 2 study testing Paclitaxel and AZD5363 in people with Metastatic Breast Cancer, run by Queen Mary University of London at 46 sites in 6 countries.
Trial summary
PAKT was an investigator-led, placebo-controlled, randomized phase II trial performed in 42 academic medical centers in the United Kindom, South Korea, France, Hungary, Romania, and Georgia. Patients were randomly assigned (1:1) to receive paclitaxel plus capivasertib or paclitaxel plus placebo. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Paclitaxel and AZD5363
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 71 participants
- Where
- 46 sitesin 6 countries
- Study dates
- 14 May 2014to 30 Jun 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Written informed consent prior to admission to this study
- Women, age > 18 years
- Histologically confirmed breast cancer
- Metastatic or locally recurrent disease; locally recurrent disease must not be amenable to resection with curative intent (patients who are considered suitable for surgical or ablative techniques following potential down-staging with study treatment are not eligible)
- Patient must have
- At least one lesion, not previously irradiated, that can be measured accurately at baseline as ≥ 10mm in the longest diameter (except lymph nodes which must have short axis ≥15mm) with CT, or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements, OR
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- lytic or mixed bone lesions in the absence of measurable disease as defined above; patients with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible.
- Radiological or clinical evidence of recurrence or progression
- Triple-negative disease
- Formalin fixed paraffin embedded tumour sample from the primary or recurrent cancer must be available for central testing
- Patients must be able to swallow and retain oral medication
- Haematologic and biochemical indices within protocol specified ranges
- ECOG performance status 0-2
- Non-childbearing potential. If patient is of childbearing potential, she must have a negative serum pregnancy test and agree to use adequate contraception
- Willing and able to provide written informed consent
Who cannot join
- Patients with confirm brain metastases or a history of primary central nervous system tumours or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases.
- Prior chemotherapy for metastatic breast cancer
- Radiotherapy with a wide field of radiation within 4 weeks before the first dose of study medication
- Prior treatment with PI3K inhibitors, AKT inhibitors or mTOR inhibitors
- Prior treatment with paclitaxel or docetaxel in the (neo)adjuvant setting within 12 months from inclusion into this study
- Pre-existing sensory or motor polyneuropathy ≥ Grade 2 according to CTCAE
Show all 18Show fewer
- Malabsorption syndrome or other condition that would interfere with enteral absorption
- Clinically significant pulmonary dysfunction
- Prolongation defined as a QTc interval >470msecs or other significant abnormalities in rhythm, conduction or morphology of resting ECG including 2nd degree (Type II) or 3rd degree AV block or bradycardia (ventricular rate <50 beats/min)
- Any factors that increase risk of QTc prolongation or risk of arrythmic events
- Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure NYHA Grade ≥2, or cardiac ejection fraction outside institutional range of normal or <50%
- Clinically significant abnormalities of glucose metabolism
- Patients with proteinuria or creatine >1.5xULN concurrent with creatinine clearance <50mL/min
- Exposure to potent inhibitors or inducers or substrates of CYP3A4 or substrates of CYP2D6 within 2 weeks before the first dose of study treatment
- Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study entry
- Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol.
- Detained persons or prisoners
- Pregnant or nursing women
Trial locations and contacts
46 sites in 6 countries.
46 sites in 6 countries
United Kingdom30 sites
Betsi Cadwaladr University Health Board
Bangor, LL57 2PW
Belfast Health and Social Care Trust
Belfast, BT9 7AB
Glan Clwyd Hospital BCU Health Board NHS Wales
Bodelwyddan, LL18 5UJ
Brighton and Sussex University Hospitals NHS Trust
Brighton, BN2 5BE
Cambridge University Hospitals NHS Foundation Trust
Cambridge, CB2 0QQ
East Kent Hospitals University NHS Foundation Trust
Canterbury, CT1 3NG
Velindre Cancer Centre
Cardiff, CF14 2TL
University Hospitals Coventry and Warwickshire NHs Trust
Coventry, CV2 2DX
NHS Lothian
Edinburgh, EH4 2XR
Medway NHS Foundation Trust
Gillingham, ME7 5NY
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN
Leeds Teaching Hospitals NHs Trust
Leeds, LS9 7TF
Barts Health NHS Trust
London, EC1M 6BQ
University College London Hospitals
London, NW1 2PG
Barking, Havering and Redbridge University Hospitals NHS Trust
London, RM7 0AG
Guys and St Thomas' NHS Foundation Trust
London, SE1 9RT
Lewisham and Greenwich NHS Trust
London, SE18 4QH
Royal Marsden NHS Foundation Trust-Fulham
London, SW3 6JJ
Imperial College Healthcare NHS Trust
London, W2 1NY
Maidstone and Tunbridge Wells NHS Trust
Maidstone, ME16 9QQ
The Christie NHS Foundation Trust
Manchester, M20 4BX
Nottingham University Hospitals NHS Trust
Nottingham, NG5 1PB
Southampton University Hospitals NHS Trust
Southampton, SO16 6YD
Southend University Hospital NHS Foundation Trust
Southend, SS0 0RY
University Hospital of North Staffordshire NHS Trust
Stoke-on-Trent, ST4 6QG
Royal Marsden - Sutton
Sutton, SM2 5PT
Abertawe Bro Margannwg University Health Board
Swansea, SA2 8QA
Royal Cornwall Hospitals NHS Trust
Truro, TR1 3LJ
Ysbyty Wrexham Maelor Hospital
Wrexham, LL18 5UJ
Yeovil District Hospital NHS Foundation Trust
Yeovil, BA21 4AT
South Korea6 sites
Chungbuk National University Hospital
Cheongju-si
National Cancer Center
Goyang-si
Asan Medical Center
Seoul
Korea University Guro Hospital
Seoul
Samsung Medical Centre
Seoul
Yonsei University Health System
Seoul
France3 sites
ICO René Gauducheau
Nantes
Centre André-lacassagne
Nice
Centre Hospitalier Prive Saint-Gregoire
Saint-Grégoire
Hungary3 sites
Országos Onkológiai Intézet
Budapest
University of Pécs - Clinical Center Institute of Oncotherapy
Pécs
Zala County Hospital Szent Rafael
Zalaegerszeg
Romania3 sites
Prof. Dr. I. Chiricuta Oncology Institute
Cluj-Napoca
Sf. Nectarie SRL Oncologie Medical Center
Craiova
Center of Oncology Euroclinic
Iași
About this study
Official title: A Phase II, Double-blind, Randomised, Placebo-controlled Study of the AKT Inhibitor AZD5363 in Combination With Paclitaxel in Triple-Negative Advanced or Metastatic Breast Cancer (PAKT).
PAKT was an investigator-led, placebo-controlled, randomized phase II trial performed in 42 academic medical centers in the United Kindom, South Korea, France, Hungary, Romania, and Georgia. Patients were randomly assigned (1:1) to receive paclitaxel plus capivasertib or paclitaxel plus placebo. Stratification was by number of metastatic sites (< 3 v ≥ 3) and interval from the end of prior adjuvant or neoadjuvant chemotherapy (≤ 12 v > 12 months v no prior chemotherapy).
Paclitaxel was administered as a once-per-week intravenous infusion of 90 mg/m2 over approximately 1 hour on days 1, 8, and 15 of each 28-day treatment cycle. Capivasertib 400 mg or placebo was administered orally twice per day on an intermittent weekly dosing schedule, with treatment on days 2 to 5 of weeks 1, 2, and 3 within each 28-day cycle. All treatments were continued until disease progression, development of unacceptable toxicity, or withdrawal of consent. If paclitaxel treatment was discontinued before disease progression, patients could continue to receive capivasertib or placebo alone. In case of adverse events (AEs), capivasertib or placebo could be reduced to 320 mg twice per day and subsequently to 240 mg twice per day. Capivasertib or placebo could be interrupted for up to 4 weeks for toxicity.
Tumor assessments included computed tomography scanning or magnetic resonance imaging of the chest, abdomen, and pelvis at baseline, every 8 weeks during treatment, and at progression. Patients who discontinued treatment for any reason other than progression were required to follow the same schedule of assessments until progression, initiation of another treatment, death, or withdrawal of consent.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Paclitaxel, AZD5363, Placebo
- Keywords
- Triple Negative Breast Cancer, Metastatic, AKT Inhibitor, Advanced, AZD5363, Paclitaxel, PAKT, Capivasertib
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaclitaxelDrug
Also called Taxol
Patient receive Once a week for three weeks - with one week off treatment
AZD5363Drug
Also called Capivasertib
Patients receive AZD5363/Placebo in an intermittent treatment schedule. Please see study arms for full information.
PlaceboDrug
Patients receive AZD5363/Placebo in an intermittent treatment schedule. Please see study arms for full information.
| Study group | Role | What they receive |
|---|---|---|
| Paclitaxel + AZD5363 | Active comparator | Paclitaxel was administered as a once-per-week intravenous infusion of 90 mg/m2 over approximately 1 hour on days 1, 8, and 15 of each 28-day treatment cycle. Capivasertib 400 mg was administered orally twice per day on an intermittent weekly dosing schedule, with treatment on days 2 to 5 of weeks 1, 2, and 3 within each 28-day cycle. Receives: Drug: Paclitaxel; Drug: AZD5363 |
| Paclitaxel + Placebo | Placebo comparator | Paclitaxel was administered as a once-per-week intravenous infusion of 90 mg/m2 over approximately 1 hour on days 1, 8, and 15 of each 28-day treatment cycle. Placebo was administered orally twice per day on an intermittent weekly dosing schedule, with treatment on days 2 to 5 of weeks 1, 2, and 3 within each 28-day cycle. Receives: Drug: Paclitaxel; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
Progression-free survival, defined as the time from the date of randomisation to the date of first documented tumour progression (using RECIST 1.1) or death from any cause, whichever occurs first.
Measured: Date of randomisation to date of first tumour progression or death (this can range on average between 3 weeks and 32 weeks).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2015 (estimated)
- Study start14 May 2014
- Primary completion30 Jun 2017
- Study completion30 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Queen Mary University of 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, Cancer Research UK
- Responsible party
- Sponsor
- Investigators
- Peter Schmid, Study chair, Queen Mary University LondonNicholas Turner, Principal investigator, Royal Marsden Hospital NHS- Institute of Cancer Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02423603
- Sponsor's protocol ID
- 009246QM
- Other IDs
- 2013-001521-43
- Acronym
- PAKT
- Status last verified
- Mar 2025
- First submitted
- 11 Jul 2014
- Last updated
- 10 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Schmid P, Abraham J, Chan S, Wheatley D, Brunt AM, Nemsadze G, Baird RD, Park YH, Hall PS, Perren T, Stein RC, Mangel L, Ferrero JM, Phillips M, Conibear J, Cortes J, Foxley A, de Bruin EC, McEwen R, Stetson D, Dougherty B, Sarker SJ, Prendergast A, McLaughlin-Callan M, Burgess M, Lawrence C, Cartwright H, Mousa K, Turner NC. Capivasertib Plus Paclitaxel Versus Placebo Plus Paclitaxel As First-Line Therapy for Metastatic Triple-Negative Breast Cancer: The PAKT Trial. J Clin Oncol. 2020 Feb 10;38(5):423-433. doi: 10.1200/JCO.19.00368. Epub 2019 Dec 16.
PubMed 31841354
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Double-blind, Randomised, Placebo-controlled Study of the AKT Inhibitor AZD5363 in Combination With Paclitaxel in Triple-Negative Advanced or Metastatic Breast Cancer (PAKT).
- ClinicalTrials.gov ID
- NCT02423603
- Acronym / sponsor ID
- PAKT / 009246QM
- Conditions
- Metastatic Breast Cancer
- Keywords
- Triple Negative Breast Cancer, Metastatic, AKT Inhibitor, Advanced, AZD5363, Paclitaxel, PAKT, Capivasertib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Collaborators
- AstraZeneca, Cancer Research UK
- Study start
- 14 May 2014 (actual)
- Primary completion
- 30 Jun 2017 (actual)
- Study completion
- 30 Jun 2024 (actual)
- First posted
- 22 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
PAKT was an investigator-led, placebo-controlled, randomized phase II trial performed in 42 academic medical centers in the United Kindom, South Korea, France, Hungary, Romania, and Georgia. Patients were randomly assigned (1:1) to receive paclitaxel plus capivasertib or paclitaxel plus placebo. Stratification was by number of metastatic sites (< 3 v ≥ 3) and interval from the end of prior adjuvant or neoadjuvant chemotherapy (≤ 12 v > 12 months v no prior chemotherapy).
Paclitaxel was administered as a once-per-week intravenous infusion of 90 mg/m2 over approximately 1 hour on days 1, 8, and 15 of each 28-day treatment cycle. Capivasertib 400 mg or placebo was administered orally twice per day on an intermittent weekly dosing schedule, with treatment on days 2 to 5 of weeks 1, 2, and 3 within each 28-day cycle. All treatments were continued until disease progression, development of unacceptable toxicity, or withdrawal of consent. If paclitaxel treatment was discontinued before disease progression, patients could continue to receive capivasertib or placebo alone. In case of adverse events (AEs), capivasertib or placebo could be reduced to 320 mg twice per day and subsequently to 240 mg twice per day. Capivasertib or placebo could be interrupted for up to 4 weeks for toxicity.
Tumor assessments included computed tomography scanning or magnetic resonance imaging of the chest, abdomen, and pelvis at baseline, every 8 weeks during treatment, and at progression. Patients who discontinued treatment for any reason other than progression were required to follow the same schedule of assessments until progression, initiation of another treatment, death, or withdrawal of consent.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Paclitaxel + AZD5363 | Active comparator | Drug: Paclitaxel, Drug: AZD5363Paclitaxel was administered as a once-per-week intravenous infusion of 90 mg/m2 over approximately 1 hour on days 1, 8, and 15 of each 28-day treatment cycle. Capivasertib 400 mg was administered orally twice per day on an intermittent weekly dosing schedule, with treatment on days 2 to 5 of weeks 1, 2, and 3 within each 28-day cycle. |
| Paclitaxel + Placebo | Placebo comparator | Drug: Paclitaxel, Drug: PlaceboPaclitaxel was administered as a once-per-week intravenous infusion of 90 mg/m2 over approximately 1 hour on days 1, 8, and 15 of each 28-day treatment cycle. Placebo was administered orally twice per day on an intermittent weekly dosing schedule, with treatment on days 2 to 5 of weeks 1, 2, and 3 within each 28-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Written informed consent prior to admission to this study
- Women, age > 18 years
- Histologically confirmed breast cancer
- Metastatic or locally recurrent disease; locally recurrent disease must not be amenable to resection with curative intent (patients who are considered suitable for surgical or ablative techniques following potential down-staging with study treatment are not eligible)
- Patient must have
Key exclusion criteria (18 listed)
- Patients with confirm brain metastases or a history of primary central nervous system tumours or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases.
- Prior chemotherapy for metastatic breast cancer
- Radiotherapy with a wide field of radiation within 4 weeks before the first dose of study medication
- Prior treatment with PI3K inhibitors, AKT inhibitors or mTOR inhibitors
- Prior treatment with paclitaxel or docetaxel in the (neo)adjuvant setting within 12 months from inclusion into this study
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 |
|---|---|---|
| PaclitaxelAlso: TaxolPatient receive Once a week for three weeks - with one week off treatment | Drug | Paclitaxel + AZD5363, Paclitaxel + Placebo |
| AZD5363Also: CapivasertibPatients receive AZD5363/Placebo in an intermittent treatment schedule. Please see study arms for full information. | Drug | Paclitaxel + AZD5363 |
| PlaceboPatients receive AZD5363/Placebo in an intermittent treatment schedule. Please see study arms for full information. | Drug | Paclitaxel + Placebo |
Primary outcome
Progression-free survival
Time frame: Date of randomisation to date of first tumour progression or death (this can range on average between 3 weeks and 32 weeks).
Progression-free survival, defined as the time from the date of randomisation to the date of first documented tumour progression (using RECIST 1.1) or death from any cause, whichever occurs first.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2025.
- Results publication: PubMed 31841354Schmid P, Abraham J, Chan S, Wheatley D, Brunt AM, Nemsadze G, Baird RD, Park YH, Hall PS, Perren T, Stein RC, Mangel L, Ferrero JM, Phillips M, Conibear J, Cortes J, Foxley A, de Bruin EC, McEwen R, Stetson D, Dougherty B, Sarker SJ, Prendergast A, McLaughlin-Callan M, Burgess M, Lawrence C, Cartwright H, Mousa K, Turner NC. Capivasertib Plus Paclitaxel Versus Placebo Plus Paclitaxel As First-Line Therapy for Metastatic Triple-Negative Breast Cancer: The PAKT Trial. J Clin Oncol. 2020 Feb 10;38(5):423-433. doi: 10.1200/JCO.19.00368. Epub 2019 Dec 16.
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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.
Peter Schmid study chair
Queen Mary University London
Nicholas Turner principal investigator
Royal Marsden Hospital NHS- Institute of Cancer Research
46 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Paclitaxel and AZD5363 in people with Metastatic Breast Cancer, run by Queen Mary University of London at 46 sites in 6 countries.
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 15 inclusion and 18 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 10 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 46 sites in United Kingdom, South Korea, France, Hungary, Romania and 1 more country. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Progression-free survival (time frame: Date of randomisation to date of first tumour progression or death (this can range on average between 3 weeks and 32 weeks).). 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 NCT02423603, 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 10 Mar 2025.