Description:
This was an open label, multi-center protocol for U.S. patients enrolled in the study of
ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone
receptor-positive, HER2-negative, high risk early breast cancer
Title
- Brief Title: Adjuvant Ribociclib With Endocrine Therapy in Hormone Receptor+/HER2- High Risk Early Breast Cancer
- Official Title: An Open Label, Multi-center Protocol for U.S. Patients Enrolled in a Study of Ribociclib With Endocrine Therapy as an Adjuvant Treatment in Patients With Hormone Receptor-positive, HER2-negative, High Risk Early Breast Cancer
Clinical Trial IDs
- ORG STUDY ID:
CLEE011G2301
- SECONDARY ID:
2014-001795-53
- NCT ID:
NCT03078751
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Ribociclib | LEE011 | Ribociclib + adjuvant endocrine therapy (ET) |
Adjuvant endocrine therapy | | Placebo + adjuvant endocrine therapy (ET) |
Placebo | | Placebo + adjuvant endocrine therapy (ET) |
Purpose
This was an open label, multi-center protocol for U.S. patients enrolled in the study of
ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone
receptor-positive, HER2-negative, high risk early breast cancer
Detailed Description
The purpose of this study was to evaluate the preliminary safety and tolerability of
ribociclib to standard adjuvant endocrine therapy (ET) in patients with hormone receptor (HR)
positive, Human Epidermal Growth Factor Receptor2 (HER2) negative high risk early breast
cancer (EBC).
Originally, this was a randomized, Phase III, double-blind, placebo-controlled, multi-center,
international study to evaluate efficacy and safety of ribociclib with ET as an adjuvant
treatment in patients with HR-positive, HER2-negative, high risk EBC.
Patients were randomized at a ratio of 1:1 to receive either ribociclib or placebo for
approximately 24 months in combination with a standard adjuvant ET with ET continued for at
least 60 months.
However, following a review of the ribociclib development program strategy, a decision was
taken to explore a different approach by initiating a single Phase III study for simplicity
of trial logistics and for the purpose of analyzing the overall population through a single
clinical trial. Therefore, this study was closed to enrollment early and was amended to be an
open label, multi-center Phase II study conducted in the US only. All randomized patients
were unblinded; patients randomized to placebo were permanently discontinued from the study
and patients randomized to ribociclib were offered the option to continue treatment with
ribociclib + ET.
The study included a screening phase (28 days), a treatment phase composed of maximum of 26
cycles of ribociclib in combination with ET (approximately 24 months) or until disease
recurrence, intolerable toxicity, withdrawal of consent, or discontinuation from the study
treatment for any other reason, whichever was earlier, and a 30 days safety follow up from
last dose of ribociclib. Ribociclib was given orally once a day on days 1 to 21 in each 28
days cycle.
Safety was assessed for each patient until 30 days after the last dose of ribociclib and
included routine safety monitoring except in case of death, loss to follow up or withdrawal
of consent.
Trial Arms
Name | Type | Description | Interventions |
---|
Ribociclib + adjuvant endocrine therapy (ET) | Experimental | Patients in this arm took Ribociclib in combination with standard adjuvant endocrine therapy.
ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen (Tamoxifen no longer permitted after protocol amendment 2) | - Ribociclib
- Adjuvant endocrine therapy
|
Placebo + adjuvant endocrine therapy (ET) | Placebo Comparator | Patients in this arm took Placebo in combination with standard adjuvant endocrine therapy. ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen | - Adjuvant endocrine therapy
- Placebo
|
Eligibility Criteria
Key Inclusion Criteria:
- Histologically confirmed unilateral primary invasive adenocarcinoma of the breast
- Estrogen receptor-positive and/or progesterone receptor-positive, HER2-negative breast
cancer
- Patient is after surgical resection of the tumor where tumor was removed completely,
with the final surgical specimen microscopic margins free from tumor and with
available archival tumor tissue from the surgical specimen
- Patient who received adjuvant chemotherapy and have AJCC 8th edition Prognostic Stage
Group III tumor; or patient who received neoadjuvant chemotherapy and have 1 or more
ipsilateral axillary lymph nodes with residual tumor metastases greater than 2.0 mm in
lymph node(-s) and residual tumor greater than 10.0 mm in breast tissue
- Patient has completed multi-agent adjuvant or neoadjuvant chemotherapy of ≥ 4 cycles
or ≥ 12 weeks which included taxanes prior to screening
- Patient has completed adjuvant radiotherapy (if indicated) prior to screening
- Patient may already have initiated adjuvant endocrine therapy (ET) at the time of
randomization, but randomization must take place within 52 weeks of date of initial
histological diagnosis of breast cancer and within 12 weeks of initiating ET
- ECOG Performance Status 0 or 1
- Adequate bone marrow and organ function
- Sodium, potassium, phosphorus, magnesium and total calcium laboratory values within
normal limits
- QTcF interval < 450 msec and mean resting heart rate 50-90 bpm
Key Exclusion Criteria:
- Prior treatment with CDK4/6 inhibitor
- Prior treatment with tamoxifen, raloxifen or aromatase inhibitors for reduction in
risk (chemoprevention) of breast cancer and/or treatment for osteoporosis within last
2 years
- Prior treatment with anthracyclines at cumulative doses of 450 mg/m² or more for
doxorubicin or 900 mg/m² or more for epirubicin
- Distant metastases of breast cancer beyond regional lymph nodes
- Patient has not recovered from clinical and laboratory acute toxicities of
chemotherapy, radiotherapy and surgery
- Clinically significant, uncontrolled heart disease and/or cardiac repolarization
abnormality, or clinically significant cardiac arrhythmias
- Uncontrolled hypertension with systolic blood pressure >160 mmHg
- Patient is currently receiving any of the prohibited substances that cannot be
discontinued 7 days prior to Cycle 1 Day 1: concomitant medications, herbal
supplements, and/or fruits and their juices that are known as strong inhibitors or
inducers of CYP3A4/5; medications that have a narrow therapeutic window and are
predominantly metabolized through CYP3A4/5; systemic corticosteroids ≤ 2 weeks prior
to starting study drug, or who have not fully recovered from side effects of such
treatment; concomitant medications with a known risk to prolong the QT interval and/or
known to cause torsades de points that cannot be discontinued or replaced by safe
alternative medication.
- Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or
breast-feed during the study
- Women of child-bearing potential unless they are using highly effective methods of
contraception during the study treatment and for 21 days after stopping the study
treatment.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of Participants With Adverse Events and Serious Adverse Events |
Time Frame: | Up to 26 months |
Safety Issue: | |
Description: | These are the number of participants who had adverse events or serious adverse events regardless of whether is was suspected to be drug-related or not |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- Hormone receptor-positive
- Estrogen and/or progesterone receptor-positive
- HER2-negative
- High risk early breast cancer
- Adjuvant
- Ribociclib
- LEE011
- CDK4/6 inhibitor
- Endocrine therapy
- Phase II
- Breast carcinoma
- Breast cancer
Last Updated
March 17, 2021