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Trial details imported from

For full trial details, please see the original record at

Registration number
Ethics application status
Date submitted
Date registered
Date last updated

Titles & IDs
Public title
Phosphatidylinositol 3-kinase (PI3K) Alpha iNhibition In Advanced Breast Cancer
Scientific title
A Phase II Exploratory, Open-label, Single Arm Study of BYL719 Monotherapy, a Selective Phosphatidylinositol 3-kinase (PI3K) Alpha Inhibitor, in Adult Patients With Advanced Breast Cancer Progressing After First Line Therapy.
Secondary ID [1] 0 0
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0

Study type
Description of intervention(s) / exposure
Treatment: Drugs - BYl719

Experimental: experimental - BYL719 350 mg orally daily until progression, undue adverse events or withdrawal of consent.

Treatment: Drugs: BYl719
Treatment: BYL719 350mg orally daily Treatment will be given daily until progression, undue adverse events or withdrawal of consent.
Dose reductions (two levels) are allowed. Each cycle is 28 days

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Primary outcome [1] 0 0
Objective response rate - The percentage of patients who achieve a complete or partial response as defined by RECIST 1.1 criteria.
Timepoint [1] 0 0
> 6 months
Secondary outcome [1] 0 0
Clinical Benefit Rate - Defined as Complete or partial responses according to RECIST 1.1 criteria or stable disease for 6 months or greater
Timepoint [1] 0 0
> 6 months
Secondary outcome [2] 0 0
Progression free survival - Defined as the time from study entry until documented disease progression
Timepoint [2] 0 0
> 6 months
Secondary outcome [3] 0 0
Safety and tolerability - Safety and tolerability will be described using frequency of significant treatment related adverse events (AEs) using CTCAE 4.0 grade =3, all Serious Adverse Events and SUSARs. Safety analysis will include all patients who have received at least one dose of the drug and will be evaluated descriptively
Timepoint [3] 0 0
> 6 months

Key inclusion criteria
- Patients eligible for inclusion in this study have to meet all of the following

- Males and females of any menopausal status

- Patient has signed the Informed Consent Form (ICF) prior to any screening procedures
being performed and is able to comply with protocol requirements

- Age = 18 years old

- Eastern Cooperative Oncology Group (ECOG) 0-2 that the investigator believes is stable
at the time of screening

- Patient has locally recurrent (incurable) or metastatic disease

- Patient is able to swallow and retain oral medication

- Known HER2 status (local lab) that is negative on IHC (IHC=0) and/or non-amplified.

- Known estrogen receptor (ER) and progesterone receptor (PR) status (local lab)

- Recent tumor tissue must be available from a metastatic or recurrent lesion for next
generation sequencing targeted gene panel

- Patients with TNBC disease (ER<1%, HER2-negative) should have documented progression
on at least one line of prior systemic therapy in the metastatic setting or within 12
months of adjuvant therapy completion. There is no limit on previous therapies. There
will be no molecular selection of these patients.

- Patients with ER-positive (ER=1%, HER2-negative) disease should have documented
progression on at least one line of prior systemic endocrine therapy in the metastatic
setting. There is no limit on previous therapies. Prior everolimus is allowed.

- Patients are defined as "PI3K abnormal" if they have documented gene mutation in
PTEN or gene amplification in EGFR, PIK3CA, PIK3R1 or loss in PTEN and INPP4B as per a
next generation targeted gene sequencing panel

- Measurable disease by RECIST v 1.1 criteria or non- measurable disease that is
clinically evaluable (bone only disease allowed if evaluable)

- Patient has adequate bone marrow and organ function assessed within 72 hours prior to
first dose:

- Absolute neutrophil count (ANC) = 1.5 x 10^9/L

- Platelets = 100 x 10^9/L

- Hemoglobin (Hgb) = 9.0 g/dL

- Serum creatinine = 1.5 x ULN

- Total serum bilirubin = 1.5 x ULN (in patients with known Gilbert's syndrome, a total
bilirubin = 3.0 x ULN with direct bilirubin = 1.5 x ULN)

- AST and ALT = 2.5 x ULN (alternatively < 5 x ULN if evidence of liver metastases)

- Fasting blood glucose = 140mg/dL or = 7.8 mmol/L
Minimum age
18 Years
Maximum age
No limit
Both males and females
Can healthy volunteers participate?
Key exclusion criteria
Patients eligible for this study must not meet any of the following criteria:

- Patient has a primary CNS tumor or CNS tumor involvement.

- However patients with metastatic CNS tumors may participate in this study if the
patient is:

- Four weeks from prior therapy completion (including radiation and surgery) to starting
study treatment

- Clinically stable with respect to the CNS tumor at the time of screening

- Not receiving steroid therapy

- Patient with diabetes mellitus (fasting glucose >120mg/dl or 6.7 mmol/L), or
documented steroid-induced diabetes mellitus

- Patient has a history of another malignancy within 2 years prior to starting study
treatment, except for cured basal cell carcinoma of the skin or excised carcinoma in
situ of the cervix.

- Patient who has not recovered to grade 1 or better (except alopecia) from related side
effects of any prior antineoplastic therapy

- Patient who has had systemic chemotherapy within 4 weeks (6 weeks for nitrosoureas or
mitomycin C) prior to study entry.

- Patient who has received radiotherapy = 4 weeks prior to starting study drugs, with
exception of palliative radiotherapy (= 2 weeks prior to starting study drugs), who
has not recovered from side effects of such therapy to baseline or Grade = 1 and/or
from whom = 30% of the bone marrow was irradiated. Target lesions should not have had
previous irradiation unless have progressed post treatment.

- Patient who has undergone major surgery = 4 weeks prior to starting study treatment or
who has not recovered from side effects of such procedure.

- Patient has a clinically significant cardiac disease or impaired cardiac function,
such as:

- Congestive heart failure (CHF) requiring treatment (New York Heart Association (NYHA)
Grade = 2), left ventricular ejection fraction (LVEF) < 50% as determined by
multi-gated acquisition (MUGA) scan or echocardiogram (ECHO)

- History or current evidence of clinically significant cardiac arrhythmias, atrial
fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome,
high-grade/complete AV-blockage

- Acute coronary syndromes (including myocardial infarction, unstable angina, coronary
artery bypass graft (CABG), coronary angioplasty, or stenting), < 3 months prior to

- QT interval adjusted according to Fredericia (QTcF) > 480 msec on screening ECG.

- Patient who has any severe and/or uncontrolled medical conditions such as:

- Active or uncontrolled severe infection,

- Liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis
(i.e. quantifiable HBV-DNA and/or positive HbsAg, quantifiable HCV-RNA)

- Known severely impaired lung function (spirometry and DLCO 50% or less of normal and
O2 saturation 88% or less at rest on room air)

- Active, bleeding diathesis;

- Uncontrolled arterial hypertension defined by blood pressure > 140/100 mm Hg at rest
(average of 3 consecutive readings 5 min apart)

- Chronic treatment with corticosteroids or other immunosuppressive agent

- Patient who is currently receiving medication with a known risk of prolonging the QT
interval or inducing Torsades de Pointes (TdP) and the treatment cannot either be
discontinued or switched to a different medication prior to starting study drug

- Patient who has participated in a prior investigational study within 30 days prior to

- Patient who is currently receiving treatment with drugs known to be moderate or strong
inhibitors or inducers of isoenzymes CYP34A or CYP2C8. The patient must have
discontinued moderate and strong inducers of both enzymes for at least one week and
must have discontinued strong and moderate inhibitors before the start of treatment.
Switching to a different medication prior to start of treatment is allowed; Refer to
Appendix 1

- Patient with impaired gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of oral BYL719 (e.g. ulcerative disease,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel

- Patient with known positive serology for human immunodeficiency virus (HIV).

- Patients who have received live attenuated vaccines within 1 week of start of study
drug and during the study. Patient should also avoid close contact with others who
have received live attenuated vaccines. Examples of live attenuated vaccines include
intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever,
varicella and TY21a typhoid vaccines.

- Pregnant or nursing (lactating) woman, where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive hCG laboratory test (> 5 mIU/mL).

- Patient who does not apply highly effective contraception during the study and through
the duration as defined below after the final dose of study treatment.

Study design
Purpose of the study
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?

Intervention assignment
Single group
Other design features
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Date of last participant enrolment
Date of last data collection
Sample size
Accrual to date
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne

Funding & Sponsors
Primary sponsor type
Peter MacCallum Cancer Centre, Australia
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Novartis Pharmaceuticals
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Brief summary
This is a phase II, exploratory, open-label, single arm study of BYL719 monotherapy, a
selective phosphatidylinositol 3-kinase (PI3K) alpha inhibitor, in adult patients with
advanced metastatic breast cancer progressing after first line therapy. Patients with
advanced hormone receptor positive tumors will be required to have an alteration of the PI3K
pathway. Those patients with advanced triple negative breast cancers are genetically
unselected for this study.
Trial website
Trial related presentations / publications
Zardavas D, Phillips WA, Loi S. PIK3CA mutations in breast cancer: reconciling findings from preclinical and clinical data. Breast Cancer Res. 2014 Jan 23;16(1):201. doi: 10.1186/bcr3605. Review.
Loi S, Michiels S, Lambrechts D, Fumagalli D, Claes B, Kellokumpu-Lehtinen PL, Bono P, Kataja V, Piccart MJ, Joensuu H, Sotiriou C. Somatic mutation profiling and associations with prognosis and trastuzumab benefit in early breast cancer. J Natl Cancer Inst. 2013 Jul 3;105(13):960-7. doi: 10.1093/jnci/djt121. Epub 2013 Jun 5.
Loi S, Haibe-Kains B, Majjaj S, Lallemand F, Durbecq V, Larsimont D, Gonzalez-Angulo AM, Pusztai L, Symmans WF, Bardelli A, Ellis P, Tutt AN, Gillett CE, Hennessy BT, Mills GB, Phillips WA, Piccart MJ, Speed TP, McArthur GA, Sotiriou C. PIK3CA mutations associated with gene signature of low mTORC1 signaling and better outcomes in estrogen receptor-positive breast cancer. Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10208-13. doi: 10.1073/pnas.0907011107. Epub 2010 May 17.
Public notes

Principal investigator
Name 0 0
Sherene Loi, MD,PhD
Address 0 0
Peter MacCallum Cancer Centre, East Melbourne, Victoria, AUSTRALIA
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
MedOnc1 Clinical Trials Unit
Address 0 0
Country 0 0
Phone 0 0
+61396561111 (ask for CTU)
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see