Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole, Based on Prior Endocrine Therapy, in Patients With PIK3CA Mutant, HR+, HER2- Advanced Breast Cancer Who Have Progressed on or After Prior Treatments

Breast Cancer Clinical Trial

— BYLieve  

Official title:

BYLieve: A Phase II, Multicenter, Open-label, Three-cohort, Non- Comparative Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole in Patients With PIK3CA Mutant, Hormone Receptor (HR) Positive, HER2-negative Advanced Breast Cancer (aBC), Who Have Progressed on or After Prior Treatments

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03056755
• Other study ID #: CBYL719X2402
• Secondary ID: 2016-004586-67
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 14, 2017
• Est. completion date: July 17, 2025

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study assessing the efficacy and safety of alpelisib plus fulvestrant or letrozole, based on prior endocrine therapy, in patients with hormone receptor (HR) positive, HER2-negative advanced breast cancer (aBC), harboring PIK3CA mutations, who have progressed on or after prior treatments.

Description:

This is a phase II, multicenter, open-label, three-cohort, non-comparative study of alpelisib plus endocrine therapy (either fulvestrant or letrozole) in patients with HR+, HER2- aBC harboring PIK3CA mutation(s) in the tumor whose disease has progressed on or after prior treatments.

The study includes two phases:

• Core Phase: includes treatment phase for all patients from First Patient First Treatment (FPFT) until 18 months post Last Patient First Treatment (LPFT) + 1 month Safety follow-up (total 19 months post LPFT)

• Extension Phase: includes treatment phase starting at the end of the treatment Core Phase up to 36 months. The extension treatment phase is only for patients who are continuing to benefit from treatment at the end of the Core Phase and are not eligible for PSDS (Post-Study Drug Supply) in their country based on local regulations. Patients will continue on their existing treatment assigned in the Core Phase. If PSDS becomes available for a patient, the patient should be discontinued from the study and access treatment via PSDS. During the Extension Phase there will be no per protocol efficacy assessments other than physician's determination as per standard of care of whether or not the patient is continuing to derive clinical benefit from the study treatment.

Patients who are benefiting from treatment and are eligible for PSDS will exit the trial at the end of the Core Phase.

After discontinuation of study treatment, all patients will be followed for safety for at least 30 days except in case of death, loss to follow-up or withdrawal of consent.

During the Core Phase only: If a patient discontinues study treatment for reasons other than documented disease progression, death, lost to follow-up, or withdrawal of consent for efficacy follow-up, tumor assessments should continue to be performed until documented disease progression, death, lost to follow-up, or withdrawn consent to efficacy follow-up or end of study (Post-treatment efficacy follow-up). Moreover, all participants will be followed for survival status (after progression) regardless of treatment discontinuation reason (except if consent is withdrawn, death or patient is lost to follow-up) until death, lost to follow-up, or withdrawal of consent for survival follow-up or end of the Core Phase

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 379
• Est. completion date: July 17, 2025
• Est. primary completion date: June 14, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Patient has adequate tumor tissue for the analysis of PIK3CA mutational status by a Novartis designated laboratory. It is recommended to provide a tumor sample collected after the most recent progression or recurrence.

• Advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy

• Patient has been confirmed as PIK3CA mutant as determined by a certified designated laboratory

• Patient has histologically and/or cytologically confirmed ER+ and/ or PgR+ BC

• Patient has confirmed, HER2-negative aBC. HER2-negative defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0, 1+ or 2+.

• Patients must be diagnosed with aBC, with documented evidence of tumor progression on or after prior treatments. No more than one prior regimen of chemotherapy for the treatment of metastatic disease is permitted. The maximum number of prior therapies for aBC or mBC is limited to two (maintenance therapies, where applicable, must be regarded as part of the main therapy). Patients must have recovered to grade 1 or better from any adverse events (except alopecia) related to previous therapy prior to study entry.

• Patient has either measurable disease, i.e. at least one measurable lesion as per RECIST v1.1 criteria or if no measurable disease is present than at least one predominantly lytic bone lesion must be present

• Patient has ECOG performance status of = 2

• Patient has adequate bone marrow function

Key Exclusion Criteria:

• Patient has received prior treatment with any PI3K inhibitors

• Patients with an established diagnosis of diabetes mellitus type I or uncontrolled type II

• Patient has a concurrent malignancy or malignancy within 3 years of study screening period, with the exception of adequately treated basal or squamous cell carcinoma, nonmelanoma skin cancer or curatively resected cervical cancer

• Patient has received radiotherapy = 4 weeks or limited field radiation for palliation = 2 weeks prior to enrollment, and who has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia)

• Patients receiving systemic corticosteroids = 2 weeks prior to treatment with alpelisib

• History of acute pancreatitis within 1 year of screening or past medical history of pancreatitis

• Patient has impaired GI function or GI disease that may affect the absorption of study drugs

• Patient has documented pneumonitis

• Patients being concurrently treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme Cytochrome P (CYP)3A within the last 5 days prior to study entry

Other inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Alpelisib
300 mg of alpelisib film-coated tablets administered orally once daily
• Fulvestrant
500 mg of fulvestrant via intramuscular injection administered on Days 1, 15 on Cycle 1 and Day 1 at each cycle thereafter. Cycle=28 days
• Letrozole
2.5 mg of letrozole film-coated tablets administered orally once daily
• Goserelin
3.6 mg of goserelin via injectable subcutaneous implant administered every 28 days. Only for men in Cohort B and premenopausal women.
• Leuprolide
7.5 mg of leuprolide via injectable intramuscular depot administered every 28 days. Only for men in cohort B and premenopausal women.

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	La Rioja
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Sante Fe
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Liege
Canada	Novartis Investigative Site	Halifax	Nova Scotia
Canada	Novartis Investigative Site	Kitchener	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Vancouver	British Columbia
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Temuco	Araucania
Denmark	Novartis Investigative Site	Odense C
Denmark	Novartis Investigative Site	Vejle
France	Novartis Investigative Site	Bordeaux
France	Novartis Investigative Site	Caen
France	Novartis Investigative Site	Lille Cedex
France	Novartis Investigative Site	Lyon
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Nice Cedex 2	Alpes Maritimes
France	Novartis Investigative Site	Saint Herblain
France	Novartis Investigative Site	Saint-Cloud	Hauts De Seine
France	Novartis Investigative Site	Strasbourg
France	Novartis Investigative Site	Toulouse
Germany	Novartis Investigative Site	Augsburg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Ulm
India	Novartis Investigative Site	Delhi
Israel	Novartis Investigative Site	Petach Tikva
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Rehovot
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Ancona	AN
Italy	Novartis Investigative Site	Bergamo	BG
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Roma	RM
Japan	Novartis Investigative Site	Osaka-city	Osaka
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Mexico	Novartis Investigative Site	Jalisco
Netherlands	Novartis Investigative Site	Maastricht	AZ
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Castellon	Comunidad Valenciana
Spain	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Salamanca	Castilla Y Leon
Spain	Novartis Investigative Site	Sevilla	Andalucia
Taiwan	Novartis Investigative Site	Tainan
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
United Kingdom	Novartis Investigative Site	Edinburgh
United Kingdom	Novartis Investigative Site	Leicester
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Nottingham
United Kingdom	Novartis Investigative Site	Sutton	Surrey
United States	New Mexico Cancer Care Alliance	Albuquerque	New Mexico
United States	Kaiser Permanente Medical Group Kaiser Permanente-Moanalua M C	Anaheim	California
United States	Greater Baltimore Medical Center Cancer Center	Baltimore	Maryland
United States	Mercy Medical Center	Baltimore	Maryland
United States	Beverly Hills Cancer Center	Beverly Hills	California
United States	St Vincent Frontier Cancer Center	Billings	Montana
United States	Massachusetts General Hospital Neuroendocrine Unit	Boston	Massachusetts
United States	Lahey Clinic	Burlington	Massachusetts
United States	Uni Hosp of Cleveland Cancer Center	Cleveland	Ohio
United States	Texas Oncology Charles A. Sammons Cancer Ctr	Dallas	Texas
United States	Josephine Ford Cancer Center Main Centre	Detroit	Michigan
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	University of Calif Irvine Med Cntr	Irvine	California
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Louisville James Graham Brown Cancer Center SC	Louisville	Kentucky
United States	Yale University Yale Cancer Center	New Haven	Connecticut
United States	Memorial Sloane Ketterin Cancer Ctr	New York	New York
United States	Virginia Oncology Associates SC	Norfolk	Virginia
United States	Advent Health Cancer Institute	Orlando	Florida
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Cancer Care Centers of South Texas HOAST CCC of So TX San Antonio 2	San Antonio	Texas
United States	UT Health San Antonio	San Antonio	Texas
United States	Kaiser Permanent Southern Californi	San Diego	California
United States	UCSF Main Centre	San Francisco	California
United States	Northwest Medical Specialists	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Canada,  Chile,  Denmark,  France,  Germany,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Core Phase: Percentage of Participants Who Were Alive Without Disease Progression at 6 Months	Percentage of participants who were alive without disease progression at 6-month follow-up based on local investigator assessment per RECIST v1.1 in Cohort A, Cohort B and Cohort C. Participants who progressed, died, or discontinued study before 6 months were counted as a failure.	At 6 months
Secondary	Core Phase: Progression Free Survival (PFS)	PFS is defined as the time from the date of first dose of study medication to the date of the first documented progression or death due to any cause occurring in the study. PFS was assessed based on local investigator's assessment according to RECIST v1.1. PFS was censored if no PFS event was observed before the cut-off date. The censoring date was the date of last adequate tumor assessment before the cut-off date. If a PFS event was observed after two or more missing or non-adequate tumor assessments, then PFS was censored at the last adequate tumor assessment.; PFS was estimated using the Kaplan-Meier method.	From date of first dose to date of first documented progression or death, up to 46 months
Secondary	Core Phase: Progression Free Survival on Next Line Treatment (PFS2)	PFS2 is defined as time from the date of first dose of study medication to the date of first documented progression on next-line therapy or death from any cause. The first documented progression on next-line treatment is based on investigator assessment of progressive disease.; PFS2 was estimated using the Kaplan-Meier method.	From date of first dose to date of first documented progression on next-line therapy or death, up to approximately 55 months
Secondary	Core Phase: Overall Response Rate (ORR)	ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST v1.1 in each cohort.; CR: Disappearance of all non-nodal target lesions and all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm and all lymph nodes assigned as non-target lesions must be non-pathological in size (<10 mm short axis) PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.	Up to 46 months
Secondary	Core Phase: Clinical Benefit Rate (CBR)	CBR is defined as the percentage of participants with a BOR of CR or PR or an overall lesion response of stable disease (SD) or Non-CR/ Non-PD lasting = 24 weeks based on local investigator's assessment according to RECIST v1.1.; CR: Disappearance of all non-nodal target lesions and all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm and all lymph nodes assigned as non-target lesions must be non-pathological in size (<10 mm short axis) PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.; SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.	Up to 46 months
Secondary	Core Phase: Duration of Response (DOR)	DOR is the time from the date of first documented response (confirmed CR or PR based on local investigator's assessment according to RECIST v1.1) to the date of first documented progression or death due to underlying cancer.; Subjects continuing without progression or death due to underlying cancer were censored at the date of their last adequate tumor assessment.; DOR was estimated using the Kaplan-Meier method.	From date of first documented response to first documented progression or death, up to 33.3 months
Secondary	Core Phase: Overall Survival (OS)	OS is defined as the time of start of treatment to date of death or lost to follow-up. If a subject was not known to have died, then the OS data was censored at the date of the last known alive status for the patient.	From date of first dose and up to approximately 55 months
Secondary	Extension Phase: Percentage of Participants With Clinical Benefit as Assessed by the Investigator During the Extension Phase	Percentage of participants with clinical benefit as assessed by the Investigator at scheduled visits during the extension phase	From end of core phase up to 12 months