PAKT: AZD5363 in Combination With Paclitaxel in Triple-Negative Advanced or Metastatic Breast Cancer

NCT02423603 | Completed Phase 2 DMC

• 2 other identifiers: 009246QM2013-001521-43
• Study Type: interventional
• Target: 71
• Locations: 6 countries
• Sites: 46

Brief 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. 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

Keywords

Triple Negative Breast Cancer; Metastatic; AKT Inhibitor; Advanced; AZD5363; Paclitaxel; PAKT; Capivasertib

Outcome Measures

Primary Outcomes (1)

• 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.

  Date of randomisation to date of first tumour progression or death (this can range on average between 3 weeks and 32 weeks).

Study Arms (2)

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.

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.

Drug: Paclitaxel; Drug: Placebo

Interventions

Paclitaxel DRUG

Patient receive Once a week for three weeks - with one week off treatment

Also known as: Taxol

Paclitaxel + AZD5363; Paclitaxel + Placebo

AZD5363 DRUG

Patients receive AZD5363/Placebo in an intermittent treatment schedule. Please see study arms for full information.

Also known as: Capivasertib

Paclitaxel + AZD5363

Placebo DRUG

Patients receive AZD5363/Placebo in an intermittent treatment schedule. Please see study arms for full information.

Paclitaxel + Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• Pre-existing sensory or motor polyneuropathy ≥ Grade 2 according to CTCAE
• 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.

Sponsors & Collaborators

• Queen Mary University of London: lead
• AstraZeneca: collaborator
• Cancer Research UK: collaborator

Study Sites (46)

ICO René Gauducheau

Nantes, France

Location

Centre André-lacassagne

Nice, France

Location

Centre Hospitalier Prive Saint-Gregoire

Saint-Grégoire, France

Location

Institute of Clinical Oncology

Tbilisi, Georgia

Location

Országos Onkológiai Intézet

Budapest, Hungary

Location

University of Pécs - Clinical Center Institute of Oncotherapy

Pécs, Hungary

Location

Zala County Hospital Szent Rafael

Zalaegerszeg, Hungary

Location

Prof. Dr. I. Chiricuta Oncology Institute

Cluj-Napoca, Romania

Location

Sf. Nectarie SRL Oncologie Medical Center

Craiova, Romania

Location

Center of Oncology Euroclinic

Iași, Romania

Location

Chungbuk National University Hospital

Cheongju-si, South Korea

Location

National Cancer Center

Goyang-si, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Korea University Guro Hospital

Seoul, South Korea

Location

Samsung Medical Centre

Seoul, South Korea

Location

Yonsei University Health System

Seoul, South Korea

Location

Betsi Cadwaladr University Health Board

Bangor, LL57 2PW, United Kingdom

Location

Belfast Health and Social Care Trust

Belfast, BT9 7AB, United Kingdom

Location

Glan Clwyd Hospital BCU Health Board NHS Wales

Bodelwyddan, LL18 5UJ, United Kingdom

Location

Brighton and Sussex University Hospitals NHS Trust

Brighton, BN2 5BE, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

East Kent Hospitals University NHS Foundation Trust

Canterbury, CT1 3NG, United Kingdom

Location

Velindre Cancer Centre

Cardiff, CF14 2TL, United Kingdom

Location

University Hospitals Coventry and Warwickshire NHs Trust

Coventry, CV2 2DX, United Kingdom

Location

NHS Lothian

Edinburgh, EH4 2XR, United Kingdom

Location

Medway NHS Foundation Trust

Gillingham, ME7 5NY, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Leeds Teaching Hospitals NHs Trust

Leeds, LS9 7TF, United Kingdom

Location

Barts Health NHS Trust

London, EC1M 6BQ, United Kingdom

Location

University College London Hospitals

London, NW1 2PG, United Kingdom

Location

Barking, Havering and Redbridge University Hospitals NHS Trust

London, RM7 0AG, United Kingdom

Location

Guys and St Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

Location

Lewisham and Greenwich NHS Trust

London, SE18 4QH, United Kingdom

Location

Royal Marsden NHS Foundation Trust-Fulham

London, SW3 6JJ, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, W2 1NY, United Kingdom

Location

Maidstone and Tunbridge Wells NHS Trust

Maidstone, ME16 9QQ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, NG5 1PB, United Kingdom

Location

Southampton University Hospitals NHS Trust

Southampton, SO16 6YD, United Kingdom

Location

Southend University Hospital NHS Foundation Trust

Southend, SS0 0RY, United Kingdom

Location

University Hospital of North Staffordshire NHS Trust

Stoke-on-Trent, ST4 6QG, United Kingdom

Location

Royal Marsden - Sutton

Sutton, SM2 5PT, United Kingdom

Location

Abertawe Bro Margannwg University Health Board

Swansea, SA2 8QA, United Kingdom

Location

Royal Cornwall Hospitals NHS Trust

Truro, TR1 3LJ, United Kingdom

Location

Ysbyty Wrexham Maelor Hospital

Wrexham, LL18 5UJ, United Kingdom

Location

Yeovil District Hospital NHS Foundation Trust

Yeovil, BA21 4AT, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 31841354 RESULT

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms; Neoplasm Metastasis

Interventions

Paclitaxel; capivasertib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Peter Schmid

  Queen Mary University London

  STUDY CHAIR

• Nicholas Turner

  Royal Marsden Hospital NHS- Institute of Cancer Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2014
• First Posted: April 22, 2015
• Study Start: May 14, 2014
• Primary Completion: June 30, 2017
• Study Completion: June 30, 2024
• Last Updated: March 10, 2025

Record last verified: 2025-03

Locations

GE (1); FR (3); HU (3); KR (6); GB (30); RO (3)