To compare invasive disease-free survival (iDFS) for ribociclib + ET versus placebo + ET in patients with HR-positive, HER2-negative, EBCwith high risk of recurrence.
ID
Source
Brief title
Condition
- Breast neoplasms benign (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Invasive disease-free survival (iDFS) using STEEP criteria
Secondary outcome
- Recurrence-free survival (RFS) using STEEP criteria
- Distant disease-free survival (DDFS) using STEEP criteria
- Overall survival (OS)
- Quality of Life (QOL)
Background summary
While adjuvant endocrine therapy (ET) is effective in reducing risk of
recurrence in patients with hormone receptor (HR)-positive early breast cancer
(EBC), recurrences are still common, especially in patients with unfavorable
clinical, pathological and/or molecular features. Ribociclib, a CDK4/6
inhibitor, demonstrated clinical efficacy with tolerable toxicity when added to
ET in patients with HR-positive, HER2-negative advanced breast cancer.
The purpose of this study is to evaluate the effect of addition of ribociclib
to standard adjuvant ET on invasive disease-free survival (iDFS) in patients
with HRpositive, HER2-negative intermediate-risk EBC.
Study objective
To compare invasive disease-free survival (iDFS) for ribociclib + ET versus
placebo + ET in patients with HR-positive, HER2-negative, EBC
with high risk of recurrence.
Study design
This is 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.
Intervention
During Treatment phase ribociclib or ribociclib matching placebo will be given
orally once a day on days 1-21 of each 28 day cycle. Days 22-28 of each cycle
will be a *rest* period from ribociclib or placebo. Endocrine therapy (ET) will
be given orally once a day on a continuous daily schedule (e.g., days 1-28 of
each 28-day cycle).
GnRH agonist, per investigator*s judgement, (examples include but not limited
to goserelin, triptorelin or leuprolide) will be given every 4 weeks for
premenopausal women only. There will be no *rest* period in the ET schedule.
Study burden and risks
Based on preclinical and clinical data, treatment of ribociclib in combination
with ET is expected to be tolerable and toxicities of the treatment are
expected to be manageable and reversible upon dose reduction, treatment
interruption or discontinuation.
Patients in this study will be carefully monitored for key toxicities that have
been observed with ribociclib or endocrine treatments. Risk will be
further minimized by adherence to inclusion/exclusion selection criteria,
avoidance of prohibited medication, close safety monitoring and dose adjustment
guidelines.
Lichtstrasse 35
Basel 4056
CH
Lichtstrasse 35
Basel 4056
CH
Listed location countries
Age
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 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 ;Additional inclusion criteria as per full protocol may apply.
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 ;Additional exclusion criteria as per full protocol may apply.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | EUCTR2014-001795-53-NL |
ClinicalTrials.gov | NCT03078751 |
CCMO | NL61281.056.17 |