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

NCT ID: NCT04544189

Last Updated: 2025-06-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-20
• Study Completion Date: 2026-03-02

Brief 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.

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.

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.

Conditions

Breast Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Alpelisib+Fulvestrant (randomized cohort)

Alpelisib (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)

Group Type: EXPERIMENTAL

Alpelisib

Intervention Type: DRUG

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

Fulvestrant

Intervention Type: DRUG

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

Placebo+Fulvestrant (randomized cohort)

Placebo (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)

Group Type: PLACEBO_COMPARATOR

Fulvestrant

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

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

PK cohort (open label cohort)

Alpelisib (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)

Group Type: EXPERIMENTAL

Alpelisib

Intervention Type: DRUG

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

Fulvestrant

Intervention Type: DRUG

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

Interventions

Alpelisib

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

Intervention Type: DRUG

Fulvestrant

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

BYL719

Eligibility Criteria

Inclusion Criteria

• 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
• 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.

Exclusion Criteria

• 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
• 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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Hefei, Anhui, China

Novartis Investigative Site

Hefei, Anhui, China

Novartis Investigative Site

Guangzhou, Guangdong, China

Novartis Investigative Site

Shijiazhuang, Hebei, China

Novartis Investigative Site

Harbin, Heilongjiang, China

Novartis Investigative Site

Zhengzhou, Henan, China

Novartis Investigative Site

Wuhan, Hubei, China

Novartis Investigative Site

Changsha, Hunan, China

Novartis Investigative Site

Nanjing, Jiangsu, China

Novartis Investigative Site

Nanjing, Jiangsu, China

Novartis Investigative Site

Nanchang, Jiangxi, China

Novartis Investigative Site

Changchun, Jilin, China

Novartis Investigative Site

Shengyang, Liaoning, China

Novartis Investigative Site

Shenyang, Liaoning, China

Novartis Investigative Site

Jinan, Shandong, China

Novartis Investigative Site

Chengdu, Sichuan, China

Novartis Investigative Site

Hangzhou, Zhejiang, China

Novartis Investigative Site

Hangzhou, Zhejiang, China

Novartis Investigative Site

Beijing, , China

Novartis Investigative Site

Bengbu, , China

Novartis Investigative Site

Dalian, , China

Novartis Investigative Site

Qingdao, , China

Novartis Investigative Site

Shanghai, , China

Novartis Investigative Site

Tianjin, , China

Countries

China

Other Identifiers

CBYL719C2201

Identifier Type: -

Identifier Source: org_study_id