AzTrials
AzTrials

Pre-menopausal Breast CancerPhase 1B-YONDNCT02058381

A Phase Ib Dose De-escalation Study With BYL719 in Premenopausal Patients With Locally Advanced or Metastatic Breast Cancer

A Phase 1 study testing alpelisib (BYL719) and buparlisib (BKM120) in people with Pre-menopausal Breast Cancer and PI3K Pathway Inhibition, run by Novartis Pharmaceuticals at 15 sites in 4 countries.

Completed

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

Official record
Search all trials

Trial summary

Based on the evidence acquired in the post-menopausal setting with everolimus and on pre-clinical evidences supporting the investigation of PI3K inhibitors, such as alpelisib and buparlisib, in combination with endocrine therapy in hormone receptor-positive MBC, the purpose of this phase Ib trial is to assess the… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
alpelisib (BYL719) and buparlisib (BKM120)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
15 sitesin 4 countries
Study dates
6 May 2014to 19 Jun 2018
Phase
Phase 1
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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient has histologically and/or cytologically confirmed diagnosis of breast cancer
  • Patient has radiological or objective evidence of inoperable locally advanced or metastatic breast cancer
  • Patient has HER2-negative breast cancer (based on most recently analyzed tumor sample)
  • Patient has ER positive and/or PgR positive breast cancer by local laboratory testing
  • Patient is premenopausal. Premenopausal status is defined as either:
  • patient had last menstrual period within the last 12 months, OR
Show all 21Show fewer
  • if on tamoxifen within the past 3 months, with a plasma estradiol ≥10 pg/mL and FSH ≤40 IU/l or in the premenopausal range, according to local laboratory definition , OR
  • in case of chemotherapy induced amenorrhea, with a plasma estradiol ≥10 pg/mL) and/or FSH ≤40 IU/l or in the premenopausal range according to local laboratory definition.
  • Patient has no previous history of endocrine therapy in the metastatic setting.
  • Note:
  • Patients who received oral endocrine therapy with duration less than 3 weeks or ≤1 injection of LHRH agonist and discontinued for a reason other than suspicious or evidence of disease progression are eligible
  • Adjuvant treatment with tamoxifen monotherapy and LHRH analogue monotherapy is allowed. Patients who received tamoxifen plus LH-RH agonist/antagonist in the adjuvant setting are eligible provided they start investigational treatment at least 12 months after the last dose of tamoxifen or LH-RH agonist/antagonist, whichever came later.
  • Patients who were already established on bisphosphonate therapy may continue on bisphosphonates.
  • Patient has received ≤1 prior chemotherapy line for MBC
  • For patient who received prior systemic therapy, radiological or objective evidence of recurrence or progression on or after the last systemic therapy is needed
  • Patient must have as per RECIST 1.1:
  • measurable disease or
  • non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease.
  • Patient has adequate bone marrow and organ function as defined by the following laboratory values:
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≦ 2 which the investigator believes is stable at the time of screening.
  • Patient has negative serum pregnancy test (β-hCG) within 72 hrs before starting study treatment.

Who cannot join

  • Patient is post-menopausal.
  • Patient has received previous endocrine treatments in the metastatic setting.
  • Patient has received previous treatment with PI3K inhibitors, AKT inhibitors, mTOR inhibitors
  • Patient has received more than one chemotherapy line for metastatic disease
  • Patient has symptomatic CNS metastases
  • Patient who has received wide field radiotherapy ≦ 4 weeks or limited field radiation for palliation ≦ 2 weeks prior to starting study drug or who have not recovered to grade 1 or better from related side effects of such therapy (with exception of alopecia alopecia)
Show all 25Show fewer
  • Patient has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy
  • Patient is currently receiving increasing or chronic treatment (> 5 days) with corticosteroids or another immunosuppressive agent, as chronic administration of corticosteroids (> 5 days) can induce CYP3A4
  • Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed
  • Patient is currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP3A. The patient must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the treatment phase is initiated.
  • Patient has a score ≧ 12 on the PHQ-9 questionnaire
  • Patient selects a response of "1, 2 or 3" to question number 9 on the PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9)
  • Patient has a GAD-7 mood scale score ≧ 15
  • Patient has a medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others) or patients with active severe personality disorders (defined according to DSM- IV) are not eligible.
  • Patient has ≧ Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
  • Patient has active cardiac disease or a history of cardiac dysfunction
  • Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
  • Patient has any of the following cardiac conduction abnormalities
  • Ventricular arrhythmias except for benign premature ventricular contractions
  • Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
  • Conduction abnormality requiring a pacemaker
  • Other cardiac arrhythmia not controlled with medication
  • Patient has a QTcF > 480 msec on the screening ECG (using the QTcF formula)
  • Patient is currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to treatment start.
  • Patient has chronic pulmonary disease including dyspnea at rest from any cause or with interstitial lung disease.

Trial locations and contacts

15 sites in 4 countries.

15 sites in 4 countries

Taiwan7 sites

  • Novartis Investigative Site

    Kaohsiung City, 83301

  • Novartis Investigative Site

    Kuei-Shan Chiang, Taoyuan/ Taiwan ROC, 33305

  • Novartis Investigative Site

    New Taipei City, TWN, 23561

  • Novartis Investigative Site

    Taichung, 407

  • Novartis Investigative Site

    Taipei, 10002

  • Novartis Investigative Site

    Taipei, 10449

  • Novartis Investigative Site

    Taipei, 112

Other trials in Taiwan

South Korea5 sites

  • Novartis Investigative Site

    Gyeonggi-do, Korea, 10408

  • Novartis Investigative Site

    Seongnam-si, Gyeonggi-do, 13620

  • Novartis Investigative Site

    Seoul, Korea, 05505

  • Novartis Investigative Site

    Seoul, Korea, 06351

  • Novartis Investigative Site

    Seoul, 03722

Other trials in South Korea

Thailand2 sites

  • Novartis Investigative Site

    Bangkok, 10330

  • Novartis Investigative Site

    Chiang Mai, 50200

Other trials in Thailand

Hong Kong1 site

  • Novartis Investigative Site

    Hong Kong

Other trials in Hong Kong

About this study

Official title: A Phase Ib Dose De-escalation Study of the Combination of Tamoxifen Plus Goserelin Acetate With Alpelisib (BYL719) or Buparlisib (BKM120) in Premenopausal Patients With Hormone Receptor-positive/HER2-negative Locally Advanced or Metastatic Breast Cancer

Based on the evidence acquired in the post-menopausal setting with everolimus and on pre-clinical evidences supporting the investigation of PI3K inhibitors, such as alpelisib and buparlisib, in combination with endocrine therapy in hormone receptor-positive MBC, the purpose of this phase Ib trial is to assess the maximum tolerated dose (MTD) and/or the RP2D(s), to characterize the safety and tolerability, to determine the single and multiple dose PK profile and assess the preliminary anti-tumor activity of alpelisib and buparlisib in combination with tamoxifen plus goserelin acetate in premenopausal hormone receptor-positive advanced breast cancer patientsgroup.

Being tested
alpelisib (BYL719), buparlisib (BKM120)

What participants receive

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

  • alpelisib (BYL719)Drug

    BYL 719 350 mg will be administered orally once daily on a continuous dosing schedule starting on day 1 (Group 1 only).

  • buparlisib (BKM120)Drug

    BKM120 100 mg will be administered orally once daily on a continuous dosing schedule starting on day 1 (Group 2 only)

Study groups in NCT02058381
Study groupRoleWhat they receive
Group 1 (alpelisib)ExperimentalAlpelisib plus Tamoxifen and Goserelin (Group 1)
Receives: Drug: alpelisib (BYL719)
Group 2 (buparlisib)ExperimentalBuparlisib plus Tamoxifen and Goserelin (Group 2)
Receives: Drug: buparlisib (BKM120)

What is being measured

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

  1. Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RP2D)

    To estimate the MTD(s) and/or the RP2D(s) of a) alpelisib in combination with tamoxifen plus goserelin acetate (Group 1) and b) buparlisib in combination with Tamoxifen plus goserelin acetate (Group 2) in premenopausal hormone receptor-positive locally advanced or MBC patients.

    Measured: 12 months

Secondary outcomes (4)

  1. Incidence, type, intensity, severity and seriousness of Adverse Events (AEs) during the first 2 cycles dose interruptions, reductions and dose intensity during the study

    To characterize the safety and tolerability of a) alpelisib in combination with tamoxifen plus goserelin acetate and b) buparlisib in combination with Tamoxifen plus goserelin acetate

    Measured: 12 months

  2. Alpelisib/buparlisib: plasma concentrations and PK parameters, including but not limited to AUC0-t, AUC0-inf, AUC0-24, Cmax, tmax, CL/F, half-life t1/2 and other PK parameters if deemed appropriate. Tamoxifen: trough plasma concentrations

    To determine the single and multiple dose PK profile of a) alpelisib in combination with tamoxifen plus goserelin acetate and b) buparlisib in combination with Tamoxifen plus goserelin acetate

    Measured: 12 months

  3. Preliminary anti-tumor activity acccording to RECIST 1.1 : It will include overall response rate, clinical benefit, progression free survival and proportion of patients who are alive without progression at 9 months from the date of treatment start

    To assess the preliminary anti-tumor activity of a) alpelisib in combination with tamoxifen plus goserelin acetate and b) buparlisib in combination with Tamoxifen plus goserelin acetate

    Measured: 12 months

  4. Index score from the EQ-5D-5L; and WPAI-GH scores for work time missed, impairment while working, overall work impairment, and activity impairment

    To evaluate and compare the impact of alpelisib and buparlisib in combination with tamoxifen plus goserelin on patient-reported health status and impact on work using the EQ-5D-5L and WPAI-GH questionnaires.

    Measured: 12 months

Timeline

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

  1. First posted10 Feb 2014 (estimated)
  2. Study start6 May 2014
  3. Primary completion19 Jun 2018
  4. Study completion19 Jun 2018

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 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02058381
Sponsor's protocol ID
CBYL719XIC01
Acronym
B-YOND
Status last verified
Dec 2018
First submitted
16 Jan 2014
Last updated
9 Mar 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Lu YS, Lee KS, Chao TY, Tseng LM, Chitapanarux I, Chen SC, Liu CT, Sohn J, Kim JH, Chang YC, Yang Y, Shotelersuk K, Jung KH, Valenti R, Slader C, Gao M, Park YH. A Phase Ib Study of Alpelisib or Buparlisib Combined with Tamoxifen Plus Goserelin in Premenopausal Women with HR-Positive HER2-Negative Advanced Breast Cancer. Clin Cancer Res. 2021 Jan 15;27(2):408-417. doi: 10.1158/1078-0432.CCR-20-1008. Epub 2020 Jul 27.

    PubMed 32718997

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing alpelisib (BYL719) and buparlisib (BKM120) in people with Pre-menopausal Breast Cancer and PI3K Pathway Inhibition, run by Novartis Pharmaceuticals at 15 sites in 4 countries.

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 21 inclusion and 25 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 9 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Taiwan, South Korea, Thailand, Hong Kong. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RP2D) (time frame: 12 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 NCT02058381, which also lists 1 linked publication.

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 9 Mar 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in