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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02506556




Registration number
NCT02506556
Ethics application status
Date submitted
22/07/2015
Date registered
23/07/2015
Date last updated
16/08/2022

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
LL14/02
Universal Trial Number (UTN)
Trial acronym
PIKNIC
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
Breast

Intervention/exposure
Study type
Interventional
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

Outcomes
Primary outcome [1] 0 0
Objective response rate
Timepoint [1] 0 0
Response is assessed from date of study enrolment every 2 cycles for the first 24 weeks and every 12 weeks after that or as clinically indicated until documented date of progression, death from any cause whichever came first assessed up to 60 months
Secondary outcome [1] 0 0
Clinical Benefit Rate
Timepoint [1] 0 0
Response is assessed from date of study enrolment every 2 cycles for the first 24 weeks and every 12 weeks after that or as clinically indicated until documented date of progression, death from any cause whichever came first assessed up to 60 months.
Secondary outcome [2] 0 0
Progression free survival
Timepoint [2] 0 0
Defined as the time from study entry until documented disease progression. Patients will be followed up for a maximum of 2 years.
Secondary outcome [3] 0 0
Safety and tolerability of BYL719
Timepoint [3] 0 0
Safety is assessed by incident of adverse events according to NCI Common Toxicity Criteria for Adverse Effects (CTCAE) version 4 though out the study from until documented one month post cessation of study medication - on average 8 months

Eligibility
Key inclusion criteria
* Patients eligible for inclusion in this study have to meet all of the following criteria:
* 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 triple negative breast cancer (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 AKT1,2,3,ALK, EGFR, ERBB2,3,4, HRAS, INPP4B, KRAS, NRAS, PTEN, PIK3CA, PIK3R1, PIK3R3, 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
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients eligible for this study must not meet any of the following criteria:

* Patient has a primary central nervous system (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 screening
* 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 hepatitis B HBV-DNA and/or positive HbsAg, quantifiable hepatitis C 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 treatment.
* Patient who has participated in a prior investigational study within 30 days prior to enrollment.
* Patient who is currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of cytochrome 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 resection).
* 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 human chorionic gonadotropin (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
Treatment
Allocation to intervention
NA
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
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/09/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/10/2021
Sample size
Target
Accrual to date
Final
38
Recruitment in Australia
Recruitment state(s)
VIC
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
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country
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

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT02506556