PAKT: AZD5363 in Combination With Paclitaxel in Triple-Negative Advanced or Metastatic Breast Cancer (PAKT)
Metastatic Breast Cancer
About this trial
This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring Triple Negative Breast Cancer, Metastatic, AKT Inhibitor, Advanced, AZD5363, Paclitaxel, PAKT, Capivasertib
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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
Sites / Locations
- ICO René Gauducheau
- Centre André-lacassagne
- Centre Hospitalier Prive Saint-Gregoire
- Institute of Clinical Oncology
- Országos Onkológiai Intézet
- University of Pécs - Clinical Center Institute of Oncotherapy
- Zala County Hospital Szent Rafael
- Chungbuk National University Hospital
- National Cancer Center
- Asan Medical Center
- Korea University Guro Hospital
- Samsung Medical Centre
- Yonsei University Health System
- Prof. Dr. I. Chiricuta Oncology Institute
- Sf. Nectarie SRL Oncologie Medical Center
- Center of Oncology Euroclinic
- Betsi Cadwaladr University Health Board
- Belfast Health and Social Care Trust
- Glan Clwyd Hospital BCU Health Board NHS Wales
- Brighton and Sussex University Hospitals NHS Trust
- Cambridge University Hospitals NHS Foundation Trust
- East Kent Hospitals University NHS Foundation Trust
- Velindre Cancer Centre
- University Hospitals Coventry and Warwickshire NHs Trust
- NHS Lothian
- Medway NHS Foundation Trust
- Beatson West of Scotland Cancer Centre
- Leeds Teaching Hospitals NHs Trust
- Barts Health NHS Trust
- University College London Hospitals
- Barking, Havering and Redbridge University Hospitals NHS Trust
- Guys and St Thomas' NHS Foundation Trust
- Lewisham and Greenwich NHS Trust
- Royal Marsden NHS Foundation Trust-Fulham
- Imperial College Healthcare NHS Trust
- Maidstone and Tunbridge Wells NHS Trust
- The Christie NHS Foundation Trust
- Nottingham University Hospitals NHS Trust
- Southampton University Hospitals NHS Trust
- Southend University Hospital NHS Foundation Trust
- University Hospital of North Staffordshire NHS Trust
- Royal Marsden - Sutton
- Abertawe Bro Margannwg University Health Board
- Royal Cornwall Hospitals NHS Trust
- Ysbyty Wrexham Maelor Hospital
- Yeovil District Hospital NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Active Comparator
Placebo Comparator
Paclitaxel + AZD5363
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. 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 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.