Resumen

The purpose of this open-label, multicenter, phase IIIb, single-arm study is to characterize the efficacy and safety of the combination of ribociclib and standard adjuvant endocrine therapy (ET) on invasive breast cancer-free survival (iBCFS), in a close to clinical practice patient population with HR-positive (HR+), HER2-negative (HER2-), Anatomic Stage Group III, IIB, and a subset of Stage IIA Early Breast Cancer (EBC).

Descripción detallada

The study consists of Screening, Treatment, and Follow-up periods. * Treatment Period: all participants who complete screening will receive ribociclib 400 mg orally once daily on days 1 to 21 of a 28-day cycle, in combination with daily ET for 36 months (approximately 39 cycles) from the date of first dose. The Treatment Period starts when the patient receives their first dose of ribociclib and ends at the time of the 30-day Safety Follow-up. All treated participants should have a Safety Follow-up call conducted 30 days after the last dose of study treatment. * Follow-up period: participants will be followed from 30 days after study treatment (i.e., ribociclib) completion/discontinuation (i.e. 30-day Safety Follow-up) until death, withdrawal of consent, lost to follow-up, or until 48 months after the last participant has received their first dose of study treatment (i.e. End of Study \[EOS\]), whichever occurs first.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 100 YearsSexo: ALL

Criterios de inclusión

Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
Participant has adequate bone marrow and organ function.
Participant is an adult, male or female ≥ 18 years of age at the time of informed consent form signature (IC).
Participant has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer (BC) based on the most recently analyzed tissue sample tested by a local laboratory prior to enrollment.
Participant has HER2- BC defined as a negative in situ hybridization test or an immunohistochemistry (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 based on the most recently analyzed tissue sample.
Participants may have already received any standard neoadjuvant and/or adjuvant ET, including tamoxifen or toremifene at the time of informed consent signature, but enrollment should occur within 36 months of prior ET start date and participants should have at least 3 years remaining of endocrine adjuvant therapy.
For participants with prior ET treatment \> 12 months, restaging is highly recommended (unless contradictory to local regulations) to rule out disease recurrence prior to enrollment.
The number of participants with prior ET between 12 and 36 months will be capped at 30%. The cap will not apply to Black or African American participants.
Participant has no contraindication to receive adjuvant ET in the study.
Participant after surgical resection where tumor was removed completely, with the final surgical specimen microscopic margins free from tumor, and belongs to one of the following categories:
Anatomic Stage Group III, or
Anatomic Stage Group IIB, or
A subset of Anatomic Stage Group IIA.
ECG values assessed by KardiaMobile-6L device, or standard 12-lead ECG per local investigator where KardiaMobile-6L cannot be used, as:
QTcF interval at Screening \< 450 msec (QT interval using Fridericia's correction).
Mean resting heart rate 50-99 beats per minute (determined from the ECG).

Criterios de exclusión

Participant with distant metastases of BC beyond regional lymph nodes (Stage IV according to AJCC 8th edition) and/or evidence of recurrence after curative surgery.
Participant is concurrently using other antineoplastic therapy with the exception of adjuvant ET.
Participant has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment, cause unacceptable safety risks, contraindicate participant participation in the clinical study or compromise compliance with the protocol, or limit life expectancy to ≤5 years.
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality.
Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the trial.
Women of child-bearing potential (CBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 21 days after stopping the treatment.

Intervenciones

drug

Ribociclib

Ribociclib 400 mg orally once daily on days 1-21 of a 28 day cycle followed by 7 days rest

drug

Letrozole

Letrozole 2.5 mg orally once daily continuously

drug

Ansastrozole

Anastrozole 1 mg orally once daily continuously.

drug

Goserelin

Goserelin administered subcutaneously at 3.6 mg once every 4 weeks if the one-month depot formulation is used or at 10.8 mg once every 3 months if the three-month depot formulation is used

drug

Leuprolide

Leuprolide administered subcutaneously at 3.75 mg once every 4 weeks if the one-month depot formulation is used or at 11.25 mg once every 3 months if the three-month depot formulation is used

drug

Exemestane

Exemestane 25 mg once daily continuously

A Phase IIIb Study to Characterize the Efficacy and Safety of Adjuvant Ribociclib Plus Endocrine Therapy in a Close-to-clinical Practice Patient Population With HR+ HER2- Early Breast Cancer (Adjuvant WIDER)

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Ribociclib

Letrozole

Ansastrozole

Goserelin

Leuprolide

Exemestane

Ubicaciones

Novartis Investigative Site

Patrocinadores

Contactos

Novartis Pharmaceuticals

Novartis Pharmaceuticals