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

NCT04544189 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CBYL719C2201
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 24

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.

Conditions

Breast Neoplasms

Keywords

Alpelisib; Fulvestrant; PIK3CA mutant advanced breast cancer; randomized cohort; PK cohort; Chinese population

Outcome Measures

Primary Outcomes (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.

  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)

• Overall survival (OS)

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

• Overall response rate (ORR)

  Up to approximately 34 months

• Clinical benefit rate (CBR) with confirmed response

  Up to approximately 34 months

• Pharmacokinetics (PK): Trough concentration of alpelisib in plasma

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

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

  Up to approximately 30 months.

Study Arms (3)

Alpelisib+Fulvestrant (randomized cohort)

EXPERIMENTAL

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)

Drug: Alpelisib; Drug: Fulvestrant

Placebo+Fulvestrant (randomized cohort)

PLACEBO COMPARATOR

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)

Drug: Fulvestrant; Drug: Placebo

PK cohort (open label cohort)

EXPERIMENTAL

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)

Drug: Alpelisib; Drug: Fulvestrant

Interventions

Alpelisib DRUG

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

Also known as: BYL719

Alpelisib+Fulvestrant (randomized cohort); PK cohort (open label cohort)

Fulvestrant 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

Alpelisib+Fulvestrant (randomized cohort); PK cohort (open label cohort); Placebo+Fulvestrant (randomized cohort)

Placebo DRUG

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

Placebo+Fulvestrant (randomized cohort)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (24)

Novartis Investigative Site

Hefei, Anhui, 230001, China

Location

Novartis Investigative Site

Hefei, Anhui, 230031, China

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510000, China

Location

Novartis Investigative Site

Shijiazhuang, Hebei, 050011, China

Location

Novartis Investigative Site

Harbin, Heilongjiang, 150081, China

Location

Novartis Investigative Site

Zhengzhou, Henan, 450008, China

Location

Novartis Investigative Site

Wuhan, Hubei, 430022, China

Location

Novartis Investigative Site

Changsha, Hunan, 410013, China

Location

Novartis Investigative Site

Nanjing, Jiangsu, 210009, China

Location

Novartis Investigative Site

Nanjing, Jiangsu, 210029, China

Location

Novartis Investigative Site

Nanchang, Jiangxi, 330009, China

Location

Novartis Investigative Site

Changchun, Jilin, 130021, China

Location

Novartis Investigative Site

Shengyang, Liaoning, 110042, China

Location

Novartis Investigative Site

Shenyang, Liaoning, 110011, China

Location

Novartis Investigative Site

Jinan, Shandong, 250117, China

Location

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310016, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310022, China

Location

Novartis Investigative Site

Beijing, 100021, China

Location

Novartis Investigative Site

Bengbu, 233004, China

Location

Novartis Investigative Site

Dalian, 116000, China

Location

Novartis Investigative Site

Qingdao, 266000, China

Location

Novartis Investigative Site

Shanghai, 200025, China

Location

Novartis Investigative Site

Tianjin, 300480, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Alpelisib; Fulvestrant

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2020
• First Posted: September 10, 2020
• Study Start: January 20, 2021
• Primary Completion (Estimated): January 29, 2027
• Study Completion (Estimated): January 29, 2027
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

CN (24)