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

NCT ID: NCT02423603

Last Updated: 2025-03-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-14
• Study Completion Date: 2024-06-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Paclitaxel + AZD5363

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.

Group Type: ACTIVE_COMPARATOR

Paclitaxel

Intervention Type: DRUG

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

AZD5363

Intervention Type: DRUG

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

Paclitaxel + Placebo

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.

Group Type: PLACEBO_COMPARATOR

Paclitaxel

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

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

Interventions

Paclitaxel

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

Intervention Type: DRUG

AZD5363

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

Taxol; Capivasertib

Eligibility Criteria

Inclusion Criteria

1. Written informed consent prior to admission to this study

2. Women, age > 18 years

3. Histologically confirmed breast cancer

4. 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)

5. 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.

6. Radiological or clinical evidence of recurrence or progression

7. Triple-negative disease

8. Formalin fixed paraffin embedded tumour sample from the primary or recurrent cancer must be available for central testing

9. Patients must be able to swallow and retain oral medication

10. Haematologic and biochemical indices within protocol specified ranges

11. ECOG performance status 0-2

12. Non-childbearing potential. If patient is of childbearing potential, she must have a negative serum pregnancy test and agree to use adequate contraception

13. Willing and able to provide written informed consent

Exclusion Criteria

1. 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.

2. Prior chemotherapy for metastatic breast cancer

3. Radiotherapy with a wide field of radiation within 4 weeks before the first dose of study medication

4. Prior treatment with PI3K inhibitors, AKT inhibitors or mTOR inhibitors

5. Prior treatment with paclitaxel or docetaxel in the (neo)adjuvant setting within 12 months from inclusion into this study

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

7. Malabsorption syndrome or other condition that would interfere with enteral absorption

8. Clinically significant pulmonary dysfunction

9. 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)

10. Any factors that increase risk of QTc prolongation or risk of arrythmic events

11. 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%

12. Clinically significant abnormalities of glucose metabolism

13. Patients with proteinuria or creatine >1.5xULN concurrent with creatinine clearance <50mL/min

14. Exposure to potent inhibitors or inducers or substrates of CYP3A4 or substrates of CYP2D6 within 2 weeks before the first dose of study treatment

15. Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study entry

16. Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol.

17. Detained persons or prisoners

18. Pregnant or nursing women

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Cancer Research UK

OTHER

Sponsor Role: collaborator

Queen Mary University of London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter Schmid

Role: STUDY_CHAIR

Queen Mary University London

Nicholas Turner

Role: PRINCIPAL_INVESTIGATOR

Royal Marsden Hospital NHS- Institute of Cancer Research

Locations

ICO René Gauducheau

Nantes, , France

Centre André-lacassagne

Nice, , France

Centre Hospitalier Prive Saint-Gregoire

Saint-Grégoire, , France

Institute of Clinical Oncology

Tbilisi, , Georgia

Országos Onkológiai Intézet

Budapest, , Hungary

University of Pécs - Clinical Center Institute of Oncotherapy

Pécs, , Hungary

Zala County Hospital Szent Rafael

Zalaegerszeg, , Hungary

Prof. Dr. I. Chiricuta Oncology Institute

Cluj-Napoca, , Romania

Sf. Nectarie SRL Oncologie Medical Center

Craiova, , Romania

Center of Oncology Euroclinic

Iași, , Romania

Chungbuk National University Hospital

Cheongju-si, , South Korea

National Cancer Center

Goyang-si, , South Korea

Asan Medical Center

Seoul, , South Korea

Korea University Guro Hospital

Seoul, , South Korea

Samsung Medical Centre

Seoul, , South Korea

Yonsei University Health System

Seoul, , South Korea

Betsi Cadwaladr University Health Board

Bangor, , United Kingdom

Belfast Health and Social Care Trust

Belfast, , United Kingdom

Glan Clwyd Hospital BCU Health Board NHS Wales

Bodelwyddan, , United Kingdom

Brighton and Sussex University Hospitals NHS Trust

Brighton, , United Kingdom

Cambridge University Hospitals NHS Foundation Trust

Cambridge, , United Kingdom

East Kent Hospitals University NHS Foundation Trust

Canterbury, , United Kingdom

Velindre Cancer Centre

Cardiff, , United Kingdom

University Hospitals Coventry and Warwickshire NHs Trust

Coventry, , United Kingdom

NHS Lothian

Edinburgh, , United Kingdom

Medway NHS Foundation Trust

Gillingham, , United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Leeds Teaching Hospitals NHs Trust

Leeds, , United Kingdom

Barts Health NHS Trust

London, , United Kingdom

University College London Hospitals

London, , United Kingdom

Barking, Havering and Redbridge University Hospitals NHS Trust

London, , United Kingdom

Guys and St Thomas' NHS Foundation Trust

London, , United Kingdom

Lewisham and Greenwich NHS Trust

London, , United Kingdom

Royal Marsden NHS Foundation Trust-Fulham

London, , United Kingdom

Imperial College Healthcare NHS Trust

London, , United Kingdom

Maidstone and Tunbridge Wells NHS Trust

Maidstone, , United Kingdom

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

Southampton University Hospitals NHS Trust

Southampton, , United Kingdom

Southend University Hospital NHS Foundation Trust

Southend, , United Kingdom

University Hospital of North Staffordshire NHS Trust

Stoke-on-Trent, , United Kingdom

Royal Marsden - Sutton

Sutton, , United Kingdom

Abertawe Bro Margannwg University Health Board

Swansea, , United Kingdom

Royal Cornwall Hospitals NHS Trust

Truro, , United Kingdom

Ysbyty Wrexham Maelor Hospital

Wrexham, , United Kingdom

Yeovil District Hospital NHS Foundation Trust

Yeovil, , United Kingdom

Countries

France; Georgia; Hungary; Romania; South Korea; United Kingdom

References

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.

Reference Type: RESULT

PMID: 31841354 (View on PubMed)

Other Identifiers

2013-001521-43

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

009246QM

Identifier Type: -

Identifier Source: org_study_id