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Metastatic Breast CancerPhase 2PIKNICNCT02506556

Phosphatidylinositol 3-kinase (PI3K) Alpha iNhibition In Advanced Breast Cancer

A Phase 2 study testing BYl719 in people with Metastatic Breast Cancer, run by Peter MacCallum Cancer Centre, Australia at 1 site in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
BYl719
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
1 siteAustralia
Study dates
7 Sep 2015to 26 Oct 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

1 site in 1 country.

Australia1 site

  • Peter MacCallum Cancer Centre

    East Melbourne, Victoria, 3002

Other trials in Australia

About this study

Official 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.

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.

Read the detailed description

The primary purpose of this study is to determine whether BYL719 is a safe and effective drug treatment for adult patients with advanced breast cancer who have progressed after first line therapy.

Who is it for? Patients may be eligible to join this study if over 18 years old, male or female, with advanced metastatic or locally recurring breast cancer which has progressed after first line therapy.

Study details All participants enrolled in this study will take the study drug, BYL719, which is a selective phosphatidylinositol 3-kinase (PI3K) alpha inhibitor. This will involve taking tablets daily.

Participants will attend regular follow-up visits for up to 2 years in order to evaluate objective response rate, clinical benefit rate, progression free survival, safety and tolerability of treatment. Regular scans and blood tests will be performed

There will be two cohorts of participants involved in this study - those with metastatic triple negative breast cancer (TNBC) and those with estrogen receptor positive and HER2 negative (ER+/HER2-) breast cancers with a genetic mutation in the PI3K pathway. Efficacy and safety of BYL719 in these patients and associations with genetic features will be evaluated in order to try to identify biomarkers of response in breast cancer.

Study medication will be continued until disease progression, unacceptable toxicity or requirement to start another anti-cancer medication.

Being tested
BYl719
Keywords
Pi3K pathway
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BYl719Drug

    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

Study groups in NCT02506556
Study groupRoleWhat they receive
experimentalExperimentalBYL719 350 mg orally daily until progression, undue adverse events or withdrawal of consent.
Receives: Drug: BYl719

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response rate

    The percentage of patients who achieve a complete or partial response as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

    Measured: 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 outcomes (3)

  1. Clinical Benefit Rate

    Defined as Complete or partial responses according to RECIST 1.1 criteria or stable disease for 6 months or greater

    Measured: 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.

  2. Progression free survival

    Defined as the time from study entry until documented disease progression

    Measured: Defined as the time from study entry until documented disease progression. Patients will be followed up for a maximum of 2 years.

  3. Safety and tolerability of BYL719

    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

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jul 2015 (estimated)
  2. Study start7 Sep 2015
  3. Primary completion26 Oct 2021
  4. Study completion26 Oct 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02506556
Sponsor's protocol ID
LL14/02
Acronym
PIKNIC
Status last verified
Apr 2022
First submitted
22 Jul 2015
Last updated
16 Aug 2022
Results posted
No
Data monitoring committee
No

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.

    PubMed 25192370

  • 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.

    PubMed 23739063

  • 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.

    PubMed 20479250

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BYl719 in people with Metastatic Breast Cancer, run by Peter MacCallum Cancer Centre, Australia at 1 site in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02506556, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2022.

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