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Advanced Breast CancerPhase 2NCT04524000

Study Assessing the Efficacy and Safety of Treatment With Alpelisib Plus Fulvestrant in Japanese Men and Postmenopausal Women With Advanced Breast Cancer

A Phase 2 study testing Alpelisib and Fulvestrant in people with Advanced Breast Cancer, run by Novartis Pharmaceuticals at 15 sites in Japan.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The purpose of this study is to assess the safety and efficacy of alpelisib plus fulvestrant in men and postmenopausal women with hormone receptor (HR) positive, human epidermal growth factor 2 (HER2)-negative, advanced breast cancer harboring a PIK3CA mutation in Japan, whose disease has progressed on or after… Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Advanced Breast Cancer
What is being tested?
Alpelisib and Fulvestrant
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
15 sitesJapan
Study dates
8 Jan 2021to 27 Feb 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Japanese man or postmenopausal woman
  • Participant has adequate tumor tissue for the analysis of PIK3CA mutational status by a Novartis designated laboratory.
  • Participant has identified PIK3CA mutation (as determined by a Novartis designated laboratory)
  • Participant has a histologically and/or cytologically confirmed diagnosis of ER+ and/or PgR+ breast cancer by local laboratory
  • Participant has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH or SISH) test is required by local laboratory testing
  • Participant has measurable disease, i.e., at least one measurable lesion as per RECIST 1.1
  • Participant has advanced breast cancer
  • Participant has ECOG performance status 0 or 1

Who cannot join

  • Participant with symptomatic visceral disease or any disease burden that makes the participant ineligible for endocrine therapy per the investigator's best judgment
  • Participant has received prior treatment;
  • with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR or AKT inhibitor for Cohort 1 and 3
  • with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR, AKT inhibitor or CDK 4/6 inhibitor for Cohort 2
  • Participant has a known hypersensitivity to alpelisib or fulvestrant, or to any of the excipients of alpelisib or fulvestrant
  • Participant with inflammatory breast cancer at screening
Show all 14Show fewer
  • Participant is concurrently using other anti-cancer therapy
  • Participant has had surgery within 14 days prior to starting study drug or has not recovered from major side effects
  • Participant with an established diagnosis at screening of diabetes mellitus type I or not controlled type II (based on FPG and HbA1c)
  • Participant has currently documented pneumonitis /interstitial lung disease
  • History of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis
  • Participant with unresolved osteonecrosis of the jaw
  • Participant has a history of severe cutaneous reactions
  • Other protocol-defined inclusion/exclusion criteria may apply

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

Japan15 sites

  • Novartis Investigative Site

    Bunkyo Ku, Tokyo, 1138677

  • Novartis Investigative Site

    Isehara, Kanagawa, 2591193

  • Novartis Investigative Site

    Kashiwa, Chiba, 2778577

  • Novartis Investigative Site

    Koto Ku, Tokyo, 1358550

  • Novartis Investigative Site

    Kumamoto, Kumamoto, 8608556

  • Novartis Investigative Site

    Meguro-ku, Tokyo, 1528902

  • Novartis Investigative Site

    Nagoya, Aichi-ken, 4648681

  • Novartis Investigative Site

    Nagoya, Aichi-ken, 4668560

  • Novartis Investigative Site

    Nagoya, Aichi-ken, 4678602

  • Novartis Investigative Site

    Niigata, 951-8566

  • Novartis Investigative Site

    Osaka, Osaka, 5400006

  • Novartis Investigative Site

    Osaka, Osaka, 5418567

  • Novartis Investigative Site

    Sendai, Miyagi, 9808574

  • Novartis Investigative Site

    Suita, Osaka, 5650871

  • Novartis Investigative Site

    Yokohama, Kanagawa, 2418515

Other trials in Japan

About this study

Official title: A Phase II Open-label, 2-Part, Multi-center Study of BYL719 (Alpelisib) in Combination With Fulvestrant for Men and Postmenopausal Women With PIK3CA Mutation Hormone Receptor (HR) Positive, HER2-negative, Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor (AI) Treatment in Japan

The purpose of this study is to assess the safety and efficacy of alpelisib plus fulvestrant in men and postmenopausal women with hormone receptor (HR) positive, human epidermal growth factor 2 (HER2)-negative, advanced breast cancer harboring a PIK3CA mutation in Japan, whose disease has progressed on or after aromatase inhibitor (AI) treatment regardless of prior CDK4/6 inhibitor use.

Read the detailed description

This is a Phase II open-label, 2-Part, multi-center study in Japan. The study will be conducted in two parts: Part 1 (Cohort 1) includes participants regardless of prior CDK4/6 inhibitor use and is designed to determine the recommended dose (RD), evaluate the tolerability and safety of alpelisib in combination with fulvestrant. Part 2 consists of 2 cohorts (the CDK4/6 inhibitor naive participants are in Cohort 2 and the CDK4/6 inhibitor pre-treated participants are in Cohort 3) which are designed to assess the efficacy and safety of alpelisib in combination with fulvestrant, will start once the RD of alpelisib is established.

Participants will be treated until disease progression, unacceptable toxicity, death or discontinuation from the study treatment for any other reason and will be followed for survival regardless of treatment discontinuation reason (except if consent is withdrawn or participant is lost to follow up).

Being tested
Alpelisib, Fulvestrant
Keywords
HR+, HER2-negative, PIK3CA mutation, Advanced breast cancer, Alpelisib, Fulvestrant, open-label, Part 1, Part 2, Japanese population

What participants receive

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

  • AlpelisibDrug

    Also called BYL719

    [Part 1] Alpelisib administered at 200 mg (DL 1), 250 mg (DL 2) or 300mg (DL 3) orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle.

    If DL 1 is tolerated, the alpelisib doses of 250 mg will be investigated. If DL 2 is tolerated, the alpelisib doses of 300 mg will be investigated.

    [Part 2] In the Part 2, participants will be enrolled into Cohort 2 (CDK4/6 inhibitor naive) and Cohort 3 (CDK4/6 inhibitor pre-treated) in parallel and alpelisib will be administered at the recommended dose identified in Part 1.

  • FulvestrantDrug

    Also called Faslodex

    Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle 1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).

Study groups in NCT04524000
Study groupRoleWhat they receive
Cohort 1:CDK4/6 inhibitor naive or pre-treated (Part 1)ExperimentalParticipants regardless of prior CDK4/6 inhibitor will be treated at escalating doses (200 mg, 250 mg and 300 mg, orally) of BYL719 in combination with Fulvestrant (500 mg, intramuscular).
Receives: Drug: Alpelisib; Drug: Fulvestrant
Cohort 2: CDK4/6 inhibitor naive (Part 2)ExperimentalParticipants who are CDK4/6 inhibitor naive will be treated with BYL719 at the recommended dose identified in Part 1 in combination with Fulvestrant (500 mg, intramuscular).
Receives: Drug: Alpelisib; Drug: Fulvestrant
Cohort 3: CDK4/6 inhibitor pre-treated (Part 2)ExperimentalParticipants who are CDK4/6 inhibitor pre-treated will be treated with BYL719 at the recommended dose identified in Part 1 in combination with Fulvestrant (500 mg, intramuscular).
Receives: Drug: Alpelisib; Drug: Fulvestrant

What is being measured

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

  1. [Part 1] The incidence of Dose Limiting Toxicities (DLTs) of alpelisib in combination with fulvestrant

    A DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 2 cycles (the first 56 days) of treatment with alpelisib in combination with fulvestrant and meets any of the criteria specified in the protocol .

    Measured: From Cycle 1 Day 1 to Cycle 2 Day 28 (Cycle = 28 days)

  2. [Part 2] Overall Response Rate (ORR) in CDK4/6 inhibitor naive participants

    ORR is defined as the proportion of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on local investigator assessment per RECIST 1.1.

    Measured: Up to approximately 36 months

Secondary outcomes (17)

  1. [Part 1] Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Safety is determined by incidence, type, and severity of adverse events per CTCAE v4.03 criteria including changes in laboratory values, vital signs, liver assessments, renal and cardiac assessments.

    Measured: Up to approximately 37 months

  2. [Part 1] Number of participants with dose adjustments

    The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) and the reasons

    Measured: Up to approximately 37 months

  3. [Part 1] Dose intensity for alpelisib and fulvestrant

    The dose intensity (computed as the ratio of actual cumulative dose received and actual duration of exposure) and the relative dose intensity (computed as the ratio of dose intensity and planned dose intensity)

    Measured: Up to approximately 37 months

  4. [Part 1] Duration of exposure for alpelisib and fulvestrant

    The duration of exposure (in months) to alpelisib and fulvestrant

    Measured: Up to approximately 37 months

  5. [Part 1] Plasma concentrations of alpelisib in combination with fulvestrant

    Summary statistics of alpelisib plasma concentrations by time point and dose level

    Measured: Cycle 1 Day 8 (pre-dose), 15 (pre-dose, post-dose 1 hour, 3 hours) and Day 1 of Cycles 2, 4, 6, 8 (pre-dose) (Cycle = 28 days)

  6. [Part 2] Overall Response Rate (ORR) for CDK4/6 inhibitor pre-treated participants

    ORR is defined as the proportion of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on local investigator assessment per RECIST 1.1.

    Measured: Up to approximately 36 months

  7. [Part 2] Progression Free Survival (PFS)

    PFS is defined as the time from the date of first administration of study treatment until the date of the first documented progression or death due to any cause. PFS will be assessed based on local investigator assessment per RECIST 1.1.

    Measured: Up to approximately 36 months

  8. [Part 2] Overall Survival (OS)

    OS is defined as the time from date of first administration of study treatment until date of death due to any cause.

    Measured: Up to approximately 60 months

  9. [Part 2] Clinical Benefit Rate (CBR)

    CBR is defined as the proportion of participants with a best overall response of confirmed CR, or confirmed PR, or an overall response of confirmed stable disease (SD), lasting for a duration of at least 24 weeks. CR, PR, and SD are defined based on local investigator assessment per RECIST 1.1.

    Measured: Up to approximately 36 months

  10. [Part 2] Duration of Response (DOR)

    DOR only applies to participants whose best overall response is CR or PR based on local investigator assessment per RECIST 1.1. The start date is the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date is defined as the date of the first documented progression or death due to underlying cancer.

    Measured: Up to approximately 36 months

  11. [Part 2] Time to Response (TTR)

    TTR is defined as the time from the date of first administration of study treatment until the date of the first documented response of either CR or PR, which must be subsequently confirmed (although date of initial response is used, not date of confirmation).

    Measured: Up to approximately 36 months

  12. [Part 2] Time to definitive deterioration of Eastern Cooperative Oncology Group (ECOG) performance status

    Time to definitive deterioration in ECOG performance status is defined as the time from the date of first administration to the date when ECOG performance status has definitively deteriorated by at least one category compared with baseline. Deterioration is considered definitive if there is no subsequent improvement in ECOG performance status back to the baseline category or above.

    Measured: Up to approximately 36 months

  13. [Part 2] Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Incidence, type, and severity of adverse events per CTCAE v4.03 criteria including changes in laboratory values, vital signs, liver assessments, renal and cardiac assessments

    Measured: Up to approximately 37 months

  14. [Part 2] Number of participants with dose adjustments

    The number and percentage of participants with dose interruptions and dose reductions

    Measured: Up to approximately 37 months

  15. [Part 2] Dose intensity for alpelisib and fulvestrant

    The dose intensity (computed as the ratio of actual cumulative dose received and actual duration of exposure) and the relative dose intensity (computed as the ratio of dose intensity and planned dose intensity)

    Measured: Up to approximately 37 months

  16. [Part 2] Duration of exposure for alpelisib and fulvestrant

    The duration of exposure (in months) to alpelisib and fulvestrant

    Measured: Up to approximately 37 months

  17. [Part 2] Plasma concentrations of alpelisib in combination with fulvestrant

    Summary statistics of alpelisib plasma concentrations by time point and dose level

    Measured: Cycle 1 Day 8 (pre-dose), 15 (pre-dose, post-dose 1 hour, 3 hours) and Day 1 of Cycles 2, 4, 6, 8 (pre-dose) (Cycle= 28 days)

Timeline

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

  1. First posted24 Aug 2020
  2. Study start8 Jan 2021
  3. Primary completion26 Feb 2027 (estimated)
  4. Study completion27 Feb 2027 (estimated)

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
Non-randomised
Intervention model
Parallel groups
Model description
Part 1 of the study has a "Single group" design and the Part 2 has a "Parallel" design.
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04524000
Sponsor's protocol ID
CBYL719C1201
Status last verified
Sep 2026
First submitted
19 Aug 2020
Last updated
18 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alpelisib and Fulvestrant in people with Advanced Breast Cancer, run by Novartis Pharmaceuticals at 15 sites in Japan.

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 8 inclusion and 14 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: under way, not looking for participants, as of the sponsor's last update on 18 Sep 2026. 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 Japan. 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?

This study is still under way. Results are not available in the source record yet.

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?

[Part 1] The incidence of Dose Limiting Toxicities (DLTs) of alpelisib in combination with fulvestrant (time frame: From Cycle 1 Day 1 to Cycle 2 Day 28 (Cycle = 28 days)). The study lists 2 primary outcomes in all. 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 NCT04524000.

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 18 Sep 2026.

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