Study of the Molecular Features of Postmenopausal Women With HR+ HER2-negative aBC on First-line Treatment With Ribociclib and Letrozole and, in Patients With a PIK3CA Mutation, on Second-line Treatment With Alpelisib Plus Fulvestrant

NCT ID: NCT03439046

Last Updated: 2024-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 287 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-02
• Study Completion Date: 2023-12-11

Brief Summary

The purpose of this clinical trial is to study of the molecular features of postmenopausal women with hormone receptor-positive (HR+) HER2-negative advanced breast cancer on first-line treatment with ribociclib and letrozole and, in patients with a PIK3CA mutation, on second-line treatment with alpelisib plus fulvestrant

Detailed Description

The main purpose of this local, multicenter study is to investigate genetic and gene expression alterations in tumor prior to and following progression on ribociclib, during core phase and then prior to and following progression on alpelisib and thus identify patterns of mutations, how they evolve, and their association with CDK4/6 inhibition and outcomes such as sustained response or early progression. The study also aims to evaluate pharmacogenomics and its association with adverse events (frequency and severity), drug-drug interactions and clinical outcomes.

Finally, the study will also generate additional long-term safety and efficacy data in this specific Italian population.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ribociclib+letrozole

Ribociclib oral (3weeks on/1week off) in combination with oral once daily letrozole: 600mg tablets ribociclib QD + 2.5 mg tablets letrozole QD

Group Type: EXPERIMENTAL

Ribociclib

Intervention Type: DRUG

Ribociclib oral (3weeks on/1week off) in combination with oral once daily letrozole: 600mg tablets ribociclib QD + 2.5 mg tablets letrozole QD

Letrozole

Intervention Type: DRUG

Ribociclib oral (3weeks on/1week off) in combination with oral once daily letrozole: 600mg tablets ribociclib QD + 2.5 mg tablets letrozole QD

alpelisib+fulvestrant

Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28 days cycle

Group Type: EXPERIMENTAL

Alpelisib

Intervention Type: DRUG

Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28 days cycle

Fulvestrant

Intervention Type: DRUG

Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28 days cycle

Interventions

Ribociclib

Ribociclib oral (3weeks on/1week off) in combination with oral once daily letrozole: 600mg tablets ribociclib QD + 2.5 mg tablets letrozole QD

Intervention Type: DRUG

Letrozole

Ribociclib oral (3weeks on/1week off) in combination with oral once daily letrozole: 600mg tablets ribociclib QD + 2.5 mg tablets letrozole QD

Intervention Type: DRUG

Alpelisib

Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28 days cycle

Intervention Type: DRUG

Fulvestrant

Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28 days cycle

Intervention Type: DRUG

Other Intervention Names

LEE011; BYL719

Eligibility Criteria

Inclusion Criteria

• Patient has an advanced (locoregionally recurrent or metastatic) breast cancer in first line treatment (treatment naïve for the advanced setting).
• Patient is in post-menopause, defined by one of the following:
• Prior bilateral oophorectomy
• Age ≥60
• Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range
• Patient has a histologically and/or cytologically confirmed diagnosis of estrogenreceptor positive and/or progesterone receptor positive breast cancer by local laboratory.
• Patient has an 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.
• Patient is willing to undergo blood and tumor sample collection for the biological assessments/objectives as scheduled in the protocol.

• Patient has been discontinued (any reason allowed) from treatment with ribociclib + letrozole in the core phase and is deemed suitable for treatment with alpelisib + fulvestrant in second line. Ribociclib + letrozole must be the last treatment regimen before alpelisib + fulvestrant.
• Patient has PIK3CA mutation as determined in tumor tissue and/or plasma by a Novartis designated laboratory. Results of tissue samples obtained during the core phase (screening or EOT) are acceptable

Exclusion Criteria

• Patient who received prior treatment with any CDK4/6 inhibitor.
• Patient who received any prior systemic hormonal therapy or chemotherapy for advanced breast cancer.

Note:

Patients who received neo/adjuvant therapy for breast cancer are eligible. If the prior neo/adjuvant therapy included letrozole or anastrozole, the disease-free interval must be greater than 12 months from the completion of treatment until study entry.

• Patients who received ≤ 28 days of letrozole or anastrozole for advanced disease prior to inclusion in this trial are eligible.

• Patient has received prior treatment with any PI3K inhibitors.
• Patient is concurrently using other anti-cancer therapy. Ribociclib and letrozole used in the core phase must be discontinued at least 7 days prior to day one of the extension study treatment.

All drugs with overlapping toxicities must be discontinued within 7 days and AE resolved to NCI CTCAE v4.03 Grade ≤1 prior to study treatment. Exception to this criterion: patients with any grade of alopecia are allowed to enter the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Novartis Investigative Site

Casale Monferrato, AL, Italy

Novartis Investigative Site

Bari, BA, Italy

Novartis Investigative Site

Bergamo, BG, Italy

Novartis Investigative Site

Benevento, BN, Italy

Novartis Investigative Site

Bologna, BO, Italy

Novartis Investigative Site

Brindisi, BR, Italy

Novartis Investigative Site

Brescia, BS, Italy

Novartis Investigative Site

Cremona, CR, Italy

Novartis Investigative Site

Catania, CT, Italy

Novartis Investigative Site

Catania, CT, Italy

Novartis Investigative Site

Cona, FE, Italy

Novartis Investigative Site

San Giovanni Rotondo, FG, Italy

Novartis Investigative Site

Genova, GE, Italy

Novartis Investigative Site

Livorno, LI, Italy

Novartis Investigative Site

Monza, MB, Italy

Novartis Investigative Site

Macerata, MC, Italy

Novartis Investigative Site

Messina, ME, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Rozzano, MI, Italy

Novartis Investigative Site

Nuoro, NU, Italy

Novartis Investigative Site

Palermo, PA, Italy

Novartis Investigative Site

Palermo, PA, Italy

Novartis Investigative Site

Padua, PD, Italy

Novartis Investigative Site

Perugia, PG, Italy

Novartis Investigative Site

Pisa, PI, Italy

Novartis Investigative Site

Aviano, PN, Italy

Novartis Investigative Site

Prato, PO, Italy

Novartis Investigative Site

Fano, PU, Italy

Novartis Investigative Site

Faenza, RA, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Salerno, SA, Italy

Novartis Investigative Site

Candiolo, TO, Italy

Novartis Investigative Site

Torino, TO, Italy

Novartis Investigative Site

Udine, UD, Italy

Novartis Investigative Site

Negrar, VR, Italy

Novartis Investigative Site

Napoli, , Italy

Novartis Investigative Site

Napoli, , Italy

Countries

Italy

Other Identifiers

2017-004176-62

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLEE011AIT01

Identifier Type: -

Identifier Source: org_study_id