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

A Phase IIIb, Open-label, Local, Multicenter Study of the Molecular Features of Postmenopausal Women With Hormone Receptor-positive (HR+) HER2-negative Advanced Breast Cancer on First-line Treatment With Ribociclib Plus Letrozole and, in Patients With a PIK3CA Mutation, on Second-line Treatment With Alpelisib Plus Fulvestrant (BioItaLEE)

ClinicalTrials.gov Identifier: NCT03439046

Novartis Reference Number: CLEE011AIT01

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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

Condition 
Breast Cancer
Phase 
Phase 3
Overall status 
Active, not recruiting
Enrollment count 
287 participants
Start date 
Feb 02, 2018
Completion date 
Nov 30, 2022
Gender 
Female
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

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

Eligibility Criteria

CORE PHASE 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.

CORE PHASE 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 is currently using other anti-cancer therapy. Other protocol-defined inclusion/exclusion criteria may apply.

EXTENSION PHASE Inclusion criteria:

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

EXTENSION PHASE Exclusion criteria:

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.

Study Locations

Italy
Novartis Investigative Site
-
Casale Monferrato, 15033
AL
Italy
Novartis Investigative Site
-
Bari, 70124
BA
Italy
Novartis Investigative Site
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Bergamo, 24127
BG
Italy
Novartis Investigative Site
-
Benevento, 82100
BN
Italy
Novartis Investigative Site
-
Brindisi, 72100
BR
Italy
Novartis Investigative Site
-
Brescia, 25123
BS
Italy
Novartis Investigative Site
-
Cremona, 26100
CR
Italy
Novartis Investigative Site
-
Catania, 95045
CT
Italy
Novartis Investigative Site
-
Catania, 95124
CT
Italy
Novartis Investigative Site
-
Cona, 44100
FE
Italy
Novartis Investigative Site
-
San Giovanni Rotondo, 71013
FG
Italy
Novartis Investigative Site
-
Genova, 16132
GE
Italy
Novartis Investigative Site
-
Livorno, 57124
LI
Italy
Novartis Investigative Site
-
Monza, 20900
MB
Italy
Novartis Investigative Site
-
Macerata, 62100
MC
Italy
Novartis Investigative Site
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Messina, 98158
ME
Italy
Novartis Investigative Site
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Milano, 20132
MI
Italy
Novartis Investigative Site
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Milano, 20133
MI
Italy
Novartis Investigative Site
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Milano, 20141
MI
Italy
Novartis Investigative Site
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Rozzano, 20089
MI
Italy
Novartis Investigative Site
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Nuoro, 08100
NU
Italy
Novartis Investigative Site
-
Palermo, 90127
PA
Italy
Novartis Investigative Site
-
Palermo, 90146
PA
Italy
Novartis Investigative Site
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Padova, 35100
PD
Italy
Novartis Investigative Site
-
Pisa, 56126
PI
Italy
Novartis Investigative Site
-
Aviano, 33081
PN
Italy
Novartis Investigative Site
-
Prato, 59100
PO
Italy
Novartis Investigative Site
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Fano, 61032
PU
Italy
Novartis Investigative Site
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Faenza, 48018
RA
Italy
Novartis Investigative Site
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Roma, 00128
RM
Italy
Novartis Investigative Site
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Roma, 00168
RM
Italy
Novartis Investigative Site
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Roma, 00189
RM
Italy
Novartis Investigative Site
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Salerno, 84131
SA
Italy
Novartis Investigative Site
-
Candiolo, 10060
TO
Italy
Novartis Investigative Site
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Torino, 10128
TO
Italy
Novartis Investigative Site
-
Udine, 33100
UD
Italy
Novartis Investigative Site
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Negrar, 37024
VR
Italy
Novartis Investigative Site
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Bologna, 40138
-
Italy
Novartis Investigative Site
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Napoli, 80131
-
Italy
Novartis Investigative Site
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Napoli, 80138
-
Italy
Novartis Investigative Site
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Perugia, 06129
-
Italy

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