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Clinical Trials List

Protocol NumberCLEE011O12301C (TRIO033)
NCT Number(ClinicalTrials.gov Identfier)NCT03701334

2019-01-01 - 2026-06-30

Phase III

Recruiting9

ICD-9233.0

Carcinoma in situ of breast

A Phase III Multi-center, Randomized, Open-label Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as an Adjuvant Treatment in Patients With Hormone Receptor-positive, HER2-negative Early Breast Cancer (New Adjuvant TriAl With Ribociclib [LEE011]: NATALEE)

  • Trial Applicant

    QPS

  • Sponsor

    Novartis Pharmaceuticals

  • Trial scale

    Multi-Regional Multi-Center

  • Update

    2025/08/20

Investigators and Locations

Principal Investigator 陳達人 Division of General Surgery
CHANGHUA CHRISTIAN HOSPITAL

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator 張源清 Division of General Surgery
MacKay Memorial Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator 鍾奇峰 Division of Hematology & Oncology
Koo Foundation Sun Yat-Sen Cancer Center

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Ling-Ming Tseng Division of General Surgery
Taipei Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Liang-Chih Liu Division of General Surgery
China Medical University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Kuo-Ting Lee Division of General Surgery
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Shin-Cheh Chen Division of General Surgery
Linkou Chang Gung Medical Foundation

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Chih-Chiang Hung Division of General Surgery
Taichung Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Chiun-Sheng Huang Division of General Surgery
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Audit

None

Condition/Disease

Hormone Receptor-positive, HER2-negative Early Breast Cancer

Objectives

Primary To compare iDFS for ribociclib + ET versus ET in patients with HR-positive, HER2-negative, EBC Secondary 1. To evaluate the two treatment arms with respect to recurrence-free survival (RFS) 2. To evaluate the two treatment arms with respect to distant disease-free survival (DDFS) 3. To evaluate the two treatment arms with respect to overall survival (OS) 4. To evaluate patient reported outcomes (PRO) for health-related quality of life (QoL) in the two treatment arms 5. To evaluate safety and tolerability of the treatment regimen 6. To characterize the pharmacokinetics (PK) of ribociclib when given in combination with NSAI (and goserelin if applicable)

Test Drug

KISQALI

Active Ingredient

Ribociclib

Dosage Form

film-coated tablet

Dosage

200 mg

Endpoints

Primary Outcome Measures :
Invasive Disease-Free Survival [ Time Frame: 44 months ]
Invasive Disease-Free Survival for ribociclib + Endocrine Therapy versus Endocrine Therapy in patients with HR-positive, HER2-negative Early Breast Cancer using STEEP criteria (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials), as assessed by Investigator


Secondary Outcome Measures :
Recurrence-free survival [ Time Frame: 44 months ]
using STEEP criteria (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials)

Distant disease-free survival [ Time Frame: 44 months ]
using STEEP criteria (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials)

Overall Survival [ Time Frame: 91 months ]
overall survival

Change from baseline in the global health status Quality of life scale score as assessed by EORTC QLQ-C30 [ Time Frame: 44 months ]
The EORTC QLQ-C30 contains functional scales, symptom scales, single items scale and a global health status/QoL scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

Change from baseline in the physical functioning sub-scale score as assessed by EORTC QLQ-C30 [ Time Frame: 44 months ]
The EORTC QLQ-C30 contains functional scales, symptom scales, single items scale and a global health status/QoL scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

PK parameter Ctrough and other applicable parameters for ribociclib [ Time Frame: 44 months ]
Pharmacokinetics of ribociclib when given in combination with Non-Steroidal Aromatase Inhibitor (and goserelin if applicable)

Inclution Criteria

1. Signed and dated Patient Informed Consent Form (PICF) obtained prior
to any trial-specific screening procedure.
2. Patient is ≥ 18 years-old at the time of PICF signature.
3. Patient is female with known menopausal status at the time of PICF
signature or initiation of adjuvant ET (whichever occurs earlier), or
male.
Postmenopausal status is defined as:
• Patient underwent bilateral oophorectomy, or
• Age ≥ 60 years, or
• Age < 60 years and amenorrhea for 12 or more months (in the
absence of chemotherapy, tamoxifen, toremifen or ovarian
suppression) and Follicle-stimulating hormone (FSH) and plasma
estradiol are in the postmenopausal ranges per local normal
ranges.
Note: for women with therapy-induced amenorrhea, serial
measurements of FSH and/or estradiol per local clinical guidelines are
required for determination of postmenopausal status.
All women who do not meet the criteria for postmenopausal status are
considered premenopausal for the purpose of this trial.
4. Patient with histologically confirmed unilateral primary invasive
adenocarcinoma of the breast with a date of initial cytologic or
histologic diagnosis within 18 months prior to randomization. Patient
with a multicentric and/or multifocal tumor is eligible if all
histopathologically examined lesions meet the pathologic criteria in
inclusion criteria 5 and 6.
5. Patient has breast cancer that is positive for ER and/or PgR according to the local laboratory as determined on the most recently analyzed
tissue sample.
6. Patient has HER2-negative breast cancer defined as a negative in situ
hybridization test or an immunohistochemistry (IHC) status of 0 or 1+. If
IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is
required to confirm the HER2-negative status (based on the most
recently analyzed tissue sample tested by a local laboratory).
7. Patient has available archival tumor tissue from the surgical specimen,
for submission to a central laboratory.
8. Patient after surgical resection where tumor was removed completely,
with the final surgical specimen microscopic margins free from tumor,
and who belongs to one of the following categories:
• Anatomic Stage Group II that is either:
• N1, or
• N0 (T2-3, N0) with G2-3 and/or Ki67≥20% (testing for Ki67 not
mandatory), excluding G1.
• Anatomic Stage Group III.
Notes:
• Patients that received neoadjuvant treatment must meet the
criteria for stage, grade, Ki67 in any presurgical staging/sample
and/or in the surgical specimen.
• Categorization into the AJCC 8th edition Anatomic Stage
Groups requires determination of the T, N and M categories.
ALND is a preferred method for axillary lymph node staging,
however SLN dissection can be used to determine the N
category as follows:
• No metastasis in SLN (patient is considered as having
pN0).
• Only micrometastasis in SLN (patient is considered as
having pN1mi).
• Patients with T1-2 and no clinically-evident nodes prior to
surgery, no neoadjuvant chemotherapy, at least one
macrometastasis in 1 or 2 SLNs, no matted nodes or gross
extranodal disease at the time of SLN dissection (patient is
considered as having pN1).
ALND is required to determine the N category in all other
patients.
9. If indicated, patient has completed adjuvant and/or neoadjuvant
chemotherapy according to the institutional guidelines, prior to
screening.
10. If indicated, patient has completed adjuvant radiotherapy according to
the institutional guidelines, prior to screening.
11. Patient has no contraindication for the adjuvant ET in the trial and is
planned to be treated with ET for 5 years (since randomization date) or more.
12. Patient may have already received any standard neo-/adjuvant ET at
the time of PICF signature, but randomization should occur within 12
months of the initial start date of ET. Ovarian suppression or short term
ET for fertility preservation is not considered neo-/adjuvant ET. If
patient was receiving tamoxifen as adjuvant ET, a washout period of 5
half-lives (i.e. 35 days) prior to randomization is required (during that
period patient can take AI).
13. Patient has an Eastern Cooperative Oncology Group (ECOG)
Performance Status of 0 or 1.
14. Patient has adequate bone marrow and organ function as defined by
the following local laboratory values:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109
/L
• Platelets ≥ 100 × 109
/L
• Hemoglobin ≥ 9.0 g/dL
• Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m2
according to the Modification of Diet in Renal Disease (MDRD)
formula
• Alanine transaminase (ALT) < 2.5 × Upper Limit Normal (ULN)
• Aspartate transaminase (AST) < 2.5 × ULN
• Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN or direct
bilirubin ≤ 1.5 × ULN in patients with well documented Gilbert’s
Syndrome
• International normalized ratio (INR) ≤ 1.5 (unless the patient is
receiving anticoagulants and the INR is within the therapeutic range
of intended use for that anticoagulant within 7 days prior to
randomization)
• Patient must have the following laboratory values within normal
limits or corrected to within normal limits with supplements (the local
laboratory value should be documented within normal limits after
the correction) before randomization:
• Sodium
• Potassium
• Phosphorus
• Magnesium
• Total Calcium (corrected for serum albumin)
15. Standard 12-lead ECG values assessed by a central laboratory, as:
• QTcF interval (using Fridericia’s correction) at screening < 450
milliseconds (msec)
• Resting heart rate 50-90 beats per minute (determined from the
ECG)
16. Patient must be willing and able to comply with scheduled visits,
treatment plans, laboratory tests, and other trial procedures.
17. Women of childbearing potential (CBP), defined as all women
physiologically capable of becoming pregnant (see Inclusion Criterion
#18 for additional information), must have confirmed negative serum
pregnancy test (for β-hCG) within 14 days prior to randomization.
18. Women of CBP must be willing to use highly effective methods of
contraception. Contraception must continue during the trial treatment
and for 21 days after stopping the treatment. Highly effective
contraception methods include:
• Total abstinence (when this is in line with the preferred and usual
lifestyle of the patient). Periodic abstinence (e.g. calendar,
ovulation, symptothermal, post-ovulation methods) and withdrawal
are not acceptable methods of contraception.
• Female sterilization (have had surgical bilateral oophorectomy with
or without hysterectomy), total hysterectomy or tubal ligation at
least 6 weeks before taking trial treatment. In case of oophorectomy
alone, only when the reproductive status of the woman has been
confirmed by follow up hormone level assessment.
• Male partner sterilization (at least 6 months prior to randomization).
For female patients on the trial the vasectomized male partner
should be the sole partner for that patient.
• Use of a combination of the following:
• Placement of an intrauterine device (IUD) or intrauterine
system (IUS), and
• Use of an occlusive cap (diaphragm or cervical/vault cap) by
the patient, or a condom by her male partner combined with a
spermicidal foam/gel/film/cream/vaginal suppository.

Exclusion Criteria

1. Patient has received any CDK4/6 inhibitor.
2. Patient has received prior treatment with tamoxifen, raloxifene or AIs for reduction in risk (“chemoprevention”) of breast cancer and/or treatment
for osteoporosis within the last 2 years prior to PICF signature.
3. Patient has received prior treatment with anthracyclines at cumulative
doses of 450 mg/m² or more for doxorubicin, or 900 mg/m² or more for
epirubicin.
4. Patient with a known hypersensitivity to any of the excipients of
ribociclib and/or ET (e.g. rare hereditary problems of galactose
intolerance, the Lapp lactase deficiency, glucose-galactose
malabsorption, and soy allergy).
5. Patient with distant metastases of breast cancer beyond regional lymph
nodes (stage IV according to AJCC 8th edition) and/or evidence of
recurrence after curative surgery.
6. Patient is concurrently using other anti-neoplastic therapy with the
exception of adjuvant ET (see Inclusion Criterion #12).
7. Patient has had major surgery, chemotherapy or radiotherapy within 14
days prior to randomization.
8. Patient has not recovered from clinical and laboratory acute toxicities
related to prior anti-cancer therapies to a NCI CTCAE (National Cancer
Institute Common Terminology Criteria for Adverse Events) version
4.03 Grade ≤1 at day of randomization. Exception to this criterion:
patients with any grade of alopecia and amenorrhea are allowed to
enter the trial.
9. Patient has a concurrent invasive malignancy or a prior invasive
malignancy whose treatment was completed within 2 years before PICF
signature. Note: Patients with prior or concurrent in situ malignancies
are eligible provided that adequate curative treatment is completed
prior to randomization.
10. Patient has known history of human immunodeficiency virus (HIV)
infection (testing is not mandatory).
11. Patient has known active hepatitis B virus (HBV) or hepatitis C virus
(HCV) infection (testing is not mandatory).
12. Clinically significant, uncontrolled heart disease and/or cardiac
repolarization abnormality, including any of the following:
• History of documented myocardial infarction (MI), angina pectoris,
symptomatic pericarditis, or coronary artery bypass graft within 6
months prior to trial entry
• Documented cardiomyopathy
• Left Ventricular Ejection Fraction (LVEF) < 50% as determined by
Multiple Gated acquisition (MUGA) scan or echocardiogram
(ECHO) (testing not mandatory)
• Long QT syndrome or family history of idiopathic sudden death or
congenital long QT syndrome, or any of the following:
• Risk factors for Torsades de Pointes (TdP) including
uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic
bradycardia
• Concomitant medication(s) with a known risk to prolong the QT
interval and/or known to cause TdP that cannot be
discontinued or replaced by safe alternative medication (e.g.
within 5 half-lives or 7 days prior to starting trial treatment)
• Inability to determine the QTcF interval
• Clinically significant cardiac arrhythmias (e.g. ventricular
tachycardia), complete left bundle branch block, high-grade
Atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II
and third degree AV block)
• Uncontrolled arterial hypertension with systolic blood pressure >
160 mmHg.
13. Patient is currently receiving any of the following substances within 7
days before randomization:
• Concomitant medications, herbal supplements, and/or fruits (e.g.
grapefruit, pummellos, starfruit, Seville oranges) 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
14. Patient is currently receiving or has received systemic corticosteroids ≤
2 weeks prior to starting trial treatment, or has not fully recovered from
side effects of such treatment.
Note: The following uses of corticosteroids are permitted: single doses,
topical applications (e.g. for rash), inhaled sprays (e.g. for obstructive
airways diseases), eye drops or local injections (e.g. intra-articular).
15. Patient has impairment of gastrointestinal (GI) function or GI disease
that may significantly alter the absorption of the oral trial treatments
(e.g. uncontrolled ulcerative diseases, uncontrolled nausea, vomiting or
diarrhea, malabsorption syndrome, or small bowel resection).
16. Patient has any other concurrent severe and/or uncontrolled medical
condition that would, in the Investigator’s judgment, cause
unacceptable safety risks, contraindicate patient participation in the
clinical trial or compromise compliance with the protocol (e.g. chronic
pancreatitis, chronic active hepatitis, liver cirrhosis or any other
significant liver disease, active untreated or uncontrolled fungal,
bacterial or viral infections, active infection requiring systemic antibacterial therapy, etc.) or limit life expectancy to ≤5 years.
17. Patient participated in another interventional study and received
treatment with an investigational product (or used an investigational
device) within 30 days prior to randomization or within 5 half-lives of the
investigational product, whichever is longer.
18. Pregnant or breast-feeding (lactating) women or women who plan to
become pregnant or breast-feed during the trial.

The Estimated Number of Participants

  • Taiwan

    165 participants

  • Global

    4400 participants

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