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)
概览
- 阶段
- 3 期
- 干预措施
- Ansastrozole
- 疾病 / 适应症
- Early Breast Cancer
- 发起方
- Novartis Pharmaceuticals
- 入组人数
- 1400
- 试验地点
- 260
- 主要终点
- Invasive Breast Cancer Free Survival (iBCFS) rate at 3 years
- 状态
- 招募中
- 最后更新
- 昨天
概览
简要总结
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).
详细描述
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.
研究者
入排标准
入选标准
- •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
排除标准
- •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.
- •Other inclusion/exclusion criteria may apply
研究组 & 干预措施
Ribociclib + endocrine therapy
Participants will receive ribociclib 400 mg orally once daily on days 1 to 21 of a 28-day cycle, in combination with daily endocrine therapy (ET) for 36 months (approximately 39 cycles). ET consists of: * For postmenopausal women: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously. * For pre/perimenopausal women, and men: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously, combined with goserelin 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) or leuprolide 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)
干预措施: Ansastrozole
Ribociclib + endocrine therapy
Participants will receive ribociclib 400 mg orally once daily on days 1 to 21 of a 28-day cycle, in combination with daily endocrine therapy (ET) for 36 months (approximately 39 cycles). ET consists of: * For postmenopausal women: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously. * For pre/perimenopausal women, and men: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously, combined with goserelin 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) or leuprolide 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)
干预措施: Ribociclib
Ribociclib + endocrine therapy
Participants will receive ribociclib 400 mg orally once daily on days 1 to 21 of a 28-day cycle, in combination with daily endocrine therapy (ET) for 36 months (approximately 39 cycles). ET consists of: * For postmenopausal women: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously. * For pre/perimenopausal women, and men: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously, combined with goserelin 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) or leuprolide 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)
干预措施: Exemestane
Ribociclib + endocrine therapy
Participants will receive ribociclib 400 mg orally once daily on days 1 to 21 of a 28-day cycle, in combination with daily endocrine therapy (ET) for 36 months (approximately 39 cycles). ET consists of: * For postmenopausal women: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously. * For pre/perimenopausal women, and men: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously, combined with goserelin 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) or leuprolide 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)
干预措施: Goserelin
Ribociclib + endocrine therapy
Participants will receive ribociclib 400 mg orally once daily on days 1 to 21 of a 28-day cycle, in combination with daily endocrine therapy (ET) for 36 months (approximately 39 cycles). ET consists of: * For postmenopausal women: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously. * For pre/perimenopausal women, and men: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously, combined with goserelin 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) or leuprolide 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)
干预措施: Letrozole
Ribociclib + endocrine therapy
Participants will receive ribociclib 400 mg orally once daily on days 1 to 21 of a 28-day cycle, in combination with daily endocrine therapy (ET) for 36 months (approximately 39 cycles). ET consists of: * For postmenopausal women: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously. * For pre/perimenopausal women, and men: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously, combined with goserelin 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) or leuprolide 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)
干预措施: Leuprolide
结局指标
主要结局
Invasive Breast Cancer Free Survival (iBCFS) rate at 3 years
时间窗: At 3 years
iBCFS is defined as the time from the date of first dose to the date of the first event of invasive ipsilateral breast tumor recurrence, local/regional invasive recurrence, distant recurrence, death (any cause), or contralateral invasive BC. iBCFS will be assessed using STEEP criteria version 2.0 (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials), as assessed by Investigator. The iBCFS rate at 3 years will be assessed.
次要结局
- Incidence and severity of adverse events (AEs) using CTCAE v4.03(Up to approximately 6 years)
- Invasive Disease-Free Survival (iDFS)(Up to approximately 6 years)
- Distant Disease-Free Survival (DDFS)(Up to approximately 6 years)
- Distant Relapse-Free Survival (DRFS)(Up to approximately 6 years)
- Recurrence-Free Interval (RFI)(Up to approximately 6 years)
- Relative dose intensity (RDI) of ribociclib(Up to 3 years)
- Overall Survival (OS)(Up to approximately 6 years)
- Time To Discontinuation (TTD) of ribociclib(Up to 3 years)
- Changes from baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) score(Up to approximately 6 years)
- Changes from baseline in Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) score(Up to approximately 6 years)
- Changes from baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) score(Up to approximately 6 years)
- Changes from baseline in European Quality of Life-5 Dimensions (EQ-5D-5L) score(Up to approximately 6 years)
- Changes from baseline in Work Productivity and Activity Impairment Questionnaire (WPAI-GH) score(Up to approximately 6 years)