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Breast NeoplasmsPhase 2NCT04544189

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

A Phase 2 study testing Alpelisib and Fulvestrant in people with Breast Neoplasms, run by Novartis Pharmaceuticals at 24 sites in China.

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 primary objective is to evaluate whether treatment with alpelisib in combination with fulvestrant prolongs Progression Free Survival (PFS) compared to treatment with placebo in combination with fulvestrant. Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Breast Neoplasms
What is being tested?
Alpelisib and Fulvestrant
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
69 participants
Where
24 sitesChina
Study dates
20 Jan 2021to 29 Jan 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

  • Participant has adequate tumor tissue for the analysis of PIK3CA mutational status by a Novartis designated laboratory. One new or recent biopsy (collected at screening if feasible) or archival tumor block or slides (3 slides minimum from a surgical specimen, or 7 slides minimum from a core needle biopsy) must be provided. It is recommended to provide a tumor sample collected after the most recent progression or recurrence.
  • Chinese man or postmenopausal woman ≥ 18 years of age
  • 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 either
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  • Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation) OR
  • If no measurable disease is present, then at least one predominantly lytic bone lesion must be present (Participants with no measurable disease and only one predominantly lytic bone lesion that has been previously irradiated are eligible if there is documented evidence of disease progression of the bone lesion after irradiation).
  • Participant has advanced (loco regionally recurrent not amenable to curative therapy or metastatic) breast cancer.
  • Participants may be:
  • relapsed with documented evidence of progression while on (neo) adjuvant endocrine therapy or within 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for metastatic disease
  • relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine therapy and then subsequently progressed with documented evidence of progression while on or after only one line of endocrine therapy for metastatic disease
  • newly diagnosed advanced breast cancer, then relapsed with documented evidence of progression while on or after only one line of endocrine therapy
  • Patient has ECOG performance status 0 or 1.
  • Patient has adequate bone marrow function.

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 (neo)adjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR or AKT inhibitor.
  • Participant has a known hypersensitivity to alpelisib or fulvestrant, or to any of the excipients of alpelisib or fulvestrant.
  • Participant has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to randomization, and who has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia) and/or from whom ≥ 25% of the bone marrow was irradiated.
  • Participant has a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
  • Participant with an established diagnosis at screening of diabetes mellitus type I or not controlled type II
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  • Participant has currently documented pneumonitis/interstitial lung disease
  • History of acute pancreatitis within 1 year of screening or a past medical history of chronic pancreatitis
  • Participant with unresolved osteonecrosis of the jaw
  • Participant has a history of severe cutaneous reactions like Stevens- Johnson-Syndrome (SJS), Erythema Multiforme (EM), or Toxic Epidermal Necrolysis (TEN), or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).
  • Other protocol-defined inclusion/exclusion criteria may apply.

Trial locations and contacts

24 sites in 1 country.

24 sites in 1 country

China24 sites

  • Novartis Investigative Site

    Beijing, 100021

  • Novartis Investigative Site

    Bengbu, 233004

  • Novartis Investigative Site

    Changchun, Jilin, 130021

  • Novartis Investigative Site

    Changsha, Hunan, 410013

  • Novartis Investigative Site

    Chengdu, Sichuan, 610041

  • Novartis Investigative Site

    Dalian, 116000

  • Novartis Investigative Site

    Guangzhou, Guangdong, 510000

  • Novartis Investigative Site

    Hangzhou, Zhejiang, 310016

  • Novartis Investigative Site

    Hangzhou, Zhejiang, 310022

  • Novartis Investigative Site

    Harbin, Heilongjiang, 150081

  • Novartis Investigative Site

    Hefei, Anhui, 230001

  • Novartis Investigative Site

    Hefei, Anhui, 230031

  • Novartis Investigative Site

    Jinan, Shandong, 250117

  • Novartis Investigative Site

    Nanchang, Jiangxi, 330009

  • Novartis Investigative Site

    Nanjing, Jiangsu, 210009

  • Novartis Investigative Site

    Nanjing, Jiangsu, 210029

  • Novartis Investigative Site

    Qingdao, 266000

  • Novartis Investigative Site

    Shanghai, 200025

  • Novartis Investigative Site

    Shengyang, Liaoning, 110042

  • Novartis Investigative Site

    Shenyang, Liaoning, 110011

  • Novartis Investigative Site

    Shijiazhuang, Hebei, 050011

  • Novartis Investigative Site

    Tianjin, 300480

  • Novartis Investigative Site

    Wuhan, Hubei, 430022

  • Novartis Investigative Site

    Zhengzhou, Henan, 450008

Other trials in China

About this study

Official title: A Phase II Randomized Double-blind, Placebo-controlled Study of Alpelisib in Combination With Fulvestrant for Chinese Men and Postmenopausal Women With Hormone Receptor Positive, HER2-negative, PIK3CA Mutant Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor (AI) Treatment, Including a Subset With Pharmacokinetic Analysis

The primary objective is to evaluate whether treatment with alpelisib in combination with fulvestrant prolongs Progression Free Survival (PFS) compared to treatment with placebo in combination with fulvestrant.

The primary scientific question of interest is: what is the treatment effect based on PFS for alpelisib in combination with fulvestrant versus placebo in combination with fulvestrant in Chinese men and postmenopausal women with HR-positive, HER2-negative advanced breast cancer with a PIK3CA mutation, who received prior treatment with an aromatase inhibitor (AI) either as (neo) adjuvant treatment or as treatment for advanced disease, regardless of study treatment discontinuation or start of new anti-neoplastic therapy.

Read the detailed description

This is a Phase II, randomized, double-blind, placebo-controlled, multi-center study conducted in Chinese men and postmenopausal women with HR- positive, HER2-negative, PIK3CA mutant advanced breast cancer which progressed on or after AI treatment. The study also includes a single arm, open-label cohort (the PK cohort) to conduct pharmacokinetic analysis.

For the randomized cohort, in the randomized treatment phase, subjects will be randomized 1:1 to receive alpelisib or matching placebo plus fulvestrant.

A total of approximately 120 subjects will be enrolled; randomization will be stratified by:

  1. Lung and/or liver metastases (yes versus no)
  2. Previous treatment with any CDK4/6 inhibitor (yes versus no) The total number of subjects pre-treated with any CDK4/6 inhibitor will be limited to 30% of the total number of subjects.

Approximately 15 subjects meeting the same inclusion/exclusion criteria as the randomized cohort will be enrolled into the PK cohort. Subjects in the PK cohort will receive alpelisib plus fulvestrant.

Subjects will continue to receive study treatment until disease progression as determined by investigator, unacceptable toxicity, or until discontinuation of study treatment due to any other reason.

Being tested
Alpelisib, Fulvestrant, Placebo
Keywords
Alpelisib, Fulvestrant, PIK3CA mutant advanced breast cancer, randomized cohort, PK cohort, Chinese population
Medical subject headings
Breast Neoplasms

What participants receive

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

  • AlpelisibDrug

    Also called BYL719

    300mg (oral) once daily, in a 28-day cycle

  • FulvestrantDrug

    Fulvestrant 500 mg (intramuscular, as two 250mg/5 mL injections) on Day 1 and 15 of Cycle 1 and on Day 1 of every Cycle thereafter

  • PlaceboDrug

    300 mg by mouth once daily, in a 28-day cycle

Study groups in NCT04544189
Study groupRoleWhat they receive
Alpelisib+Fulvestrant (randomized cohort)ExperimentalAlpelisib (300 mg by mouth once daily, in a 28-day cycle) plus fulvestrant (500 mg intramuscular [as two 250mg/5 ml injections] on Day 1 and 15 of Cycle 1 and on Day 1 of every Cycle thereafter)
Receives: Drug: Alpelisib; Drug: Fulvestrant
Placebo+Fulvestrant (randomized cohort)Placebo comparatorPlacebo (300 mg by mouth once daily, in a 28-day cycle) plus fulvestrant (500 mg intramuscular [as two 250mg/5 ml injections] on Day 1 and 15 of Cycle 1 and on Day 1 of every Cycle thereafter)
Receives: Drug: Fulvestrant; Drug: Placebo
PK cohort (open label cohort)ExperimentalAlpelisib (300 mg by mouth once daily, in a 28-day cycle) plus fulvestrant (500 mg intramuscular [as two 250mg/5 ml injections] on Day 1 and 15 of Cycle 1 and on Day 1 of every Cycle thereafter)
Receives: Drug: Alpelisib; Drug: Fulvestrant

What is being measured

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

  1. Progression Free Survival (PFS)

    PFS is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. The primary analysis for PFS will be performed based on local radiology assessment according to RECIST 1.1.

    Measured: From the date of randomization to the date of the first documented progression or death due to any cause, up to approximately 34 months

Secondary outcomes (13)

  1. Overall survival (OS)

    OS is defined as the time from date of randomization to date of death due to any cause. OS will be analyzed in the FAS population according to the randomized treatment arm and strata assigned at randomization.

    Measured: From date of randomization to date of death due to any cause, up to approximately 48 months.

  2. Overall response rate (ORR)

    Overall response rate (ORR) with confirmed response is defined as the proportion of subjects with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on local investigator's assessment according to RECIST 1.1

    Measured: Up to approximately 34 months

  3. Clinical benefit rate (CBR) with confirmed response

    CBR is defined as the proportion of subjects with a best overall response of confirmed complete response (CR), or confirmed partial response (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 as per local review according to RECIST 1.1.

    Measured: Up to approximately 34 months

  4. Pharmacokinetics (PK): Trough concentration of alpelisib in plasma

    Pre-dose concentration of alpelisib at steady state on planed days. Measurement of alpelisib will be performed only in subjects randomized to the alpelisib arm.

    Measured: Predose at Cycle (C) 1 Day (D) 15, C2 D1, C4 D1 and C6 D1 (Cycle=28 days)

  5. Time to definitive deterioration in Eastern Cooperative Oncology Group (ECOG) performance status (PS)

    PS will be assessed using ECOG scale. The scale consists of 4 grades (from 0 to 4) where 0 implies fully active and 4 implies completely disabled. Subjects will be censored if no definitive deterioration in ECOG PS is observed before the analysis cut-off date. The censoring date will be the date of the last PS assessment prior to cut- off. (Approximately up to 30 months)

    Measured: Up to approximately 30 months.

  6. Number of participants with Adverse Events (AEs)

    Incidence, type, and severity of AEs per CTCAE version 4.03 criteria including changes in laboratory values, vital signs, liver assessments and cardiac assessments

    Measured: From date of randomization until the end of the study, up to approximately 48 months

  7. Number of participants with dose interruptions

    Tolerability measured by the number of subjects who have interruptions of study treatment

    Measured: Up to approximately 30 months

  8. Number of participants with dose reductions

    Tolerability measured by the number of subjects who have reductions of study treatment.

    Measured: Up to approximately 30 months

  9. Dose intensity

    Tolerability measured by the dose intensity of study drug

    Measured: Up to approximately 30 months

  10. PFS based on local radiology assessments and using RECIST 1.1 criteria by PIK3CA mutation status measured in baseline ctDNA

    PFS defined as the time from the date of randomization to the date of the first documented progression based on local radiology assessment and according to RECIST 1.1 or death due to any cause. Results will be presented by PIK3CA mutation status measured in baseline ctDNA

    Measured: Baseline and from randomization up to approximately 34 months

  11. Pharmacokinetics (PK) of alpelisib when given in combination with fulvestrant (PK cohort): Maximum observed plasma concentration (Cmax)

    Blood samples are collected at indicated time-points for analysis of Cmax in PK cohort.

    Measured: Cycle (C) 1 Day (D) 1 and 15 pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post-dose; and pre-dose on C2D1, C4D1 and C6D1

  12. Pharmacokinetics (PK) of alpelisib when given in combination with fulvestrant (PK cohort): Time to reach maximum plasma concentration (Tmax)

    Blood samples are collected at indicated time-points for analysis of Tmax in PK cohort.

    Measured: Cycle (C) 1 Day (D) 1 and 15 pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post-dose; and pre-dose on C2D1, C4D1 and C6D1

  13. Pharmacokinetics (PK) of alpelisib when given in combination with fulvestrant (PK cohort): Area under the curve from time 0 to 24h (AUC0-24h)

    Blood samples are collected at indicated time-points for analysis of AUC0-24h in PK cohort

    Measured: Cycle (C) 1 Day (D) 1 and 15 pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post-dose; and pre-dose on C2D1, C4D1 and C6D1

Timeline

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

  1. First posted10 Sep 2020
  2. Study start20 Jan 2021
  3. Primary completion29 Jan 2027 (estimated)
  4. Study completion29 Jan 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
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
69 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04544189
Sponsor's protocol ID
CBYL719C2201
Status last verified
Sep 2026
First submitted
3 Sep 2020
Last updated
18 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
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 Breast Neoplasms, run by Novartis Pharmaceuticals at 24 sites in China.

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 15 inclusion and 11 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 24 sites in China. 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. Some participants in this study may receive a placebo. 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?

Progression Free Survival (PFS) (time frame: From the date of randomization to the date of the first documented progression or death due to any cause, up to approximately 34 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 NCT04544189.

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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