Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04524000
Recruitment Status : Recruiting
First Posted : August 24, 2020
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Advanced Breast Cancer Drug: Alpelisib Drug: Fulvestrant Phase 2

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other reason and will be followed for survival regardless of treatment discontinuation reason (except if consent is withdrawn or participant is lost to follow up).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Part 1 of the study has a "Single group" design and the Part 2 has a "Parallel" design.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : October 30, 2020
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : February 1, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Fulvestrant

Arm Intervention/treatment
Experimental: Cohort 1:CDK4/6 inhibitor naive or pre-treated (Part 1)
Participants 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).
Drug: Alpelisib

[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.

Other Name: BYL719

Drug: Fulvestrant
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).
Other Name: Faslodex

Experimental: Cohort 2: CDK4/6 inhibitor naive (Part 2)
Participants 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).
Drug: Alpelisib

[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.

Other Name: BYL719

Drug: Fulvestrant
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).
Other Name: Faslodex

Experimental: Cohort 3: CDK4/6 inhibitor pre-treated (Part 2)
Participants 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).
Drug: Alpelisib

[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.

Other Name: BYL719

Drug: Fulvestrant
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).
Other Name: Faslodex




Primary Outcome Measures :
  1. [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) ]
    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 .

  2. [Part 2] Overall Response Rate (ORR) in CDK4/6 inhibitor naive participants [ Time Frame: Up to approximately 36 months ]
    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.


Secondary Outcome Measures :
  1. [Part 1] Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to approximately 37 months ]
    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.

  2. [Part 1] Number of participants with dose adjustments [ Time Frame: Up to approximately 37 months ]
    The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) and the reasons

  3. [Part 1] Dose intensity for alpelisib and fulvestrant [ Time Frame: Up to approximately 37 months ]
    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)

  4. [Part 1] Duration of exposure for alpelisib and fulvestrant [ Time Frame: Up to approximately 37 months ]
    The duration of exposure (in months) to alpelisib and fulvestrant

  5. [Part 1] Plasma concentrations of alpelisib in combination with fulvestrant [ Time Frame: 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) ]
    Summary statistics of alpelisib plasma concentrations by time point and dose level

  6. [Part 2] Overall Response Rate (ORR) for CDK4/6 inhibitor pre-treated participants [ Time Frame: Up to approximately 36 months ]
    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.

  7. [Part 2] Progression Free Survival (PFS) [ Time Frame: Up to approximately 36 months ]
    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.

  8. [Part 2] Overall Survival (OS) [ Time Frame: Up to approximately 60 months ]
    OS is defined as the time from date of first administration of study treatment until date of death due to any cause.

  9. [Part 2] Clinical Benefit Rate (CBR) [ Time Frame: Up to approximately 36 months ]
    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.

  10. [Part 2] Duration of Response (DOR) [ Time Frame: Up to approximately 36 months ]
    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.

  11. [Part 2] Time to Response (TTR) [ Time Frame: Up to approximately 36 months ]
    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).

  12. [Part 2] Time to definitive deterioration of Eastern Cooperative Oncology Group (ECOG) performance status [ Time Frame: Up to approximately 36 months ]
    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.

  13. [Part 2] Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to approximately 37 months ]
    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

  14. [Part 2] Number of participants with dose adjustments [ Time Frame: Up to approximately 37 months ]
    The number and percentage of participants with dose interruptions and dose reductions

  15. [Part 2] Dose intensity for alpelisib and fulvestrant [ Time Frame: Up to approximately 37 months ]
    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)

  16. [Part 2] Duration of exposure for alpelisib and fulvestrant [ Time Frame: Up to approximately 37 months ]
    The duration of exposure (in months) to alpelisib and fulvestrant

  17. [Part 2] Plasma concentrations of alpelisib in combination with fulvestrant [ Time Frame: 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) ]
    Summary statistics of alpelisib plasma concentrations by time point and dose level



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04524000


Contacts
Layout table for location contacts
Contact: Novartis Pharmaceuticals +81337978748 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals

Locations
Layout table for location information
Japan
Novartis Investigative Site Recruiting
Yokohama-city, Kanagawa, Japan, 241-8515
Novartis Investigative Site Recruiting
Osaka-city, Osaka, Japan, 540-0006
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04524000    
Other Study ID Numbers: CBYL719C1201
First Posted: August 24, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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


Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
HR+
HER2-negative
PIK3CA mutation
Advanced breast cancer
Alpelisib
Fulvestrant
open-label
Part 1
Part 2
Japanese population
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs