Clinical trial NCT04524000: Study Assessing the Efficacy and Safety of Treatment With Alpelisib Plus Fulvestrant in Japanese Men and Postmenopausal Women With Advanced Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Advanced Breast Cancer
Keywords: HR+
HER2-negative
PIK3CA mutation
Advanced breast cancer
Alpelisib
Fulvestrant
open-label
Part 1
Part 2
Japanese population
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-08-24
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1 of the study has a "Single group" design and the Part 2 has a "Parallel" design.
Primary purpose: TREATMENT

Brief 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 aromatase inhibitor (AI) treatment regardless of prior CDK4/6 inhibitor use.

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any other reason and will be followed for survival regardless of treatment discontinuation reason (except if consent is withdrawn or participant is lost to follow up).

Eligibility criteria: Inclusion Criteria:

* 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

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 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
* 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

Primary outcomes:
measure: [Part 1] The incidence of Dose Limiting Toxicities (DLTs) of alpelisib in combination with fulvestrant
timeFrame: From Cycle 1 Day 1 to Cycle 2 Day 28 (Cycle = 28 days)
measure: [Part 2] Overall Response Rate (ORR) in CDK4/6 inhibitor naive participants
timeFrame: Up to approximately 36 months
Secondary outcomes:
measure: [Part 1] Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 37 months
measure: [Part 1] Number of participants with dose adjustments
timeFrame: Up to approximately 37 months
measure: [Part 1] Dose intensity for alpelisib and fulvestrant
timeFrame: Up to approximately 37 months
measure: [Part 1] Duration of exposure for alpelisib and fulvestrant
timeFrame: Up to approximately 37 months
measure: [Part 1] Plasma concentrations of alpelisib in combination with fulvestrant
timeFrame: 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)
measure: [Part 2] Overall Response Rate (ORR) for CDK4/6 inhibitor pre-treated participants
timeFrame: Up to approximately 36 months
measure: [Part 2] Progression Free Survival (PFS)
timeFrame: Up to approximately 36 months
measure: [Part 2] Overall Survival (OS)
timeFrame: Up to approximately 60 months
measure: [Part 2] Clinical Benefit Rate (CBR)
timeFrame: Up to approximately 36 months
measure: [Part 2] Duration of Response (DOR)
timeFrame: Up to approximately 36 months
measure: [Part 2] Time to Response (TTR)
timeFrame: Up to approximately 36 months
measure: [Part 2] Time to definitive deterioration of Eastern Cooperative Oncology Group (ECOG) performance status
timeFrame: Up to approximately 36 months
measure: [Part 2] Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 37 months
measure: [Part 2] Number of participants with dose adjustments
timeFrame: Up to approximately 37 months
measure: [Part 2] Dose intensity for alpelisib and fulvestrant
timeFrame: Up to approximately 37 months
measure: [Part 2] Duration of exposure for alpelisib and fulvestrant
timeFrame: Up to approximately 37 months
measure: [Part 2] Plasma concentrations of alpelisib in combination with fulvestrant
timeFrame: 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)
Other outcomes:
Locations:
city: Nagoya-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Kashiwa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Isehara
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Sendai city
country: Japan
facility: Novartis Investigative Site
state: Miyagi
city: Osaka-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Osaka-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Suita
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Bunkyo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Koto ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Meguro-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Kumamoto
country: Japan
facility: Novartis Investigative Site
city: Niigata
country: Japan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: