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

NCT02506556 | Completed Phase 2

• 1 other identifier: LL14/02
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Breast Cancer

Keywords

Pi3K pathway

Outcome Measures

Primary Outcomes (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.

  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)

• Clinical Benefit Rate

  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.

• Progression free survival

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

• Safety and tolerability of BYL719

  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

Study Arms (1)

experimental

EXPERIMENTAL

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

Drug: BYl719

Interventions

BYl719 DRUG

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

experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Peter MacCallum Cancer Centre

East Melbourne, Victoria, 3002, Australia

Location

Related Publications (3)

• 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.

  PMID: 25192370 BACKGROUND

• 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.

  PMID: 23739063 BACKGROUND

• 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.

  PMID: 20479250 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Alpelisib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Sherene Loi, MD,PhD

  Peter MacCallum Cancer Centre, East Melbourne, Victoria, AUSTRALIA

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2015
• First Posted: July 23, 2015
• Study Start: September 7, 2015
• Primary Completion: October 26, 2021
• Study Completion: October 26, 2021
• Last Updated: August 16, 2022

Record last verified: 2022-04

Locations

AU (1)