Clinical Trials List
Protocol NumberCLEE011A2404
NCT Number(ClinicalTrials.gov Identfier)NCT02941926
2017-09-21 - 2020-12-31
Phase III
Terminated5
ICD-10C50
Malignant neoplasm of breast
An open-label, multicenter, Phase IIIb study to assess the safety and efficacy of ribociclib (LEE011) in combination with letrozole for the treatment of men and pre/postmenopausal women with hormone receptor-positive (HR+) HER2-negative (HER2-) advanced breast cancer (aBC) with no prior hormonal therapy for advanced disease
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Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
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Sponsor
Novartis Pharmaceuticals
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- HWEI-CHUNG WANG Division of General Surgery
- Yao-Chung Wu Division of General Surgery
- Liang-Chih Liu Division of General Surgery
- Ming-Hung Tsai Division of Hematology & Oncology
- Chih-Jung Chen Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Ya-Ting Hsu Division of Hematology & Oncology
- Wu-Chou Su Division of Hematology & Oncology
- Yao-Lung Kuo Division of General Surgery
- Kuo-Ting Lee Division of General Surgery
- Ya-Ping Chen Division of Hematology & Oncology
- Jui-Hung Tsai Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
5 Terminated
Audit
None
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Advanced Breast Cancer
Objectives
The purpose of this Phase IIIb study is to collect additional safety and efficacy data for the combination of ribociclib + letrozole in men and pre/postmenopausal women with HR+HER2- advanced breast cancer.
Test Drug
Ribociclib (LEE011)/ Letrozole/Goserelin
Active Ingredient
Goserelin
Letrozole
Ribociclib
Letrozole
Ribociclib
Dosage Form
Tablet
Tablet
Injection
Tablet
Injection
Dosage
200 mg
2.5mg
3.6 mg
2.5mg
3.6 mg
Endpoints
Primary Outcome Measures:
1. Number of participants with adverse events (AEs) and Serious AEs (SAEs) as a measure of safety and tolerability (Core phase).
Secondary Outcome Measures:
1. Time-to-Progression (TTP) (Core phase).
2. Overall response rate (ORR) for patients with measurable disease (Core phase).
3. Clinical Benefit Rate (CBR) (Core phase).
4. Functional Assessment Cancer Therapy- Breast (FACT-B) questionnaire scores (Core phase).
5. Change from baseline in FACT-B scores (Core phase).
6. Number of participants with AEs and SAEs as a measure of safety and tolerability (Extension phase).
7. Percentage of patients with clinical benefit (Extension phase).
1. Number of participants with adverse events (AEs) and Serious AEs (SAEs) as a measure of safety and tolerability (Core phase).
Secondary Outcome Measures:
1. Time-to-Progression (TTP) (Core phase).
2. Overall response rate (ORR) for patients with measurable disease (Core phase).
3. Clinical Benefit Rate (CBR) (Core phase).
4. Functional Assessment Cancer Therapy- Breast (FACT-B) questionnaire scores (Core phase).
5. Change from baseline in FACT-B scores (Core phase).
6. Number of participants with AEs and SAEs as a measure of safety and tolerability (Extension phase).
7. Percentage of patients with clinical benefit (Extension phase).
Inclution Criteria
1. Male or female advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.
2. In the case of women, both pre/perimenopausal and postmenopausal patients are allowed to be included in this study; menopausal status is relevant for the requirement of goserelin to be used concomitantly with ribociclib and letrozole.
(1) Postmenopausal status is defined either by:
I). Prior bilateral oophorectomy OR ii). Age ≥ 60 OR iii). Age < 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range. If patient is taking tamoxifen or toremifene and age < 60, then FSH and plasma estradiol levels should be in post-menopausal range per local normal range (NCCN Guidelines version 2.2017).
Note: For women with therapy-induced amenorrhea, serial measurements of FSH and/or estradiol are needed to ensure menopausal status.
(2) Premenopausal status is defined as either:
I). Patient had last menstrual period within the last 12 months, OR ii). If on tamoxifen or toremifene within the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range, OR iii). In case of therapy induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal range per local normal range.
(3) Perimenopausal status is define as neither premenopausal nor postmenopausal Note: Throughout this document, perimenopausal and premenopausal status is grouped together and referred as "Premenopausal"
3. Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
4. Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an 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.
5. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2
6. Patient has adequate bone marrow and organ function as defined by ALL of the following laboratory values (as assessed by local laboratory):
(1) Absolute neutrophil count ≥ 1.5 × 10^9/L
(2) Platelets ≥ 100 × 10^9/L
(3) Hemoglobin ≥ 9.0 g/dL
(4) Potassium, sodium, calcium corrected for serum albumin and magnesium within normal limits or corrected to within normal limits with supplements before first dose of the study medication
(5) INR ≤1.5
(6) Serum creatinine <1.5 mg/dl or creatinine clearance≥50 mL/min
(7) In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be below 2.5 × ULN. If the patient has liver metastases, ALT and AST should be < 5 × ULN.
(8) Total serum bilirubin < ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in patients with well-documented Gilbert's Syndrome
7. Patient must have a 12-lead ECG with ALL of the following parameters at screening:
(1) QTcF interval at screening <450 msec (using Fridericia's correction)
(2) Resting heart rate ≥ 50 bpm
2. In the case of women, both pre/perimenopausal and postmenopausal patients are allowed to be included in this study; menopausal status is relevant for the requirement of goserelin to be used concomitantly with ribociclib and letrozole.
(1) Postmenopausal status is defined either by:
I). Prior bilateral oophorectomy OR ii). Age ≥ 60 OR iii). Age < 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range. If patient is taking tamoxifen or toremifene and age < 60, then FSH and plasma estradiol levels should be in post-menopausal range per local normal range (NCCN Guidelines version 2.2017).
Note: For women with therapy-induced amenorrhea, serial measurements of FSH and/or estradiol are needed to ensure menopausal status.
(2) Premenopausal status is defined as either:
I). Patient had last menstrual period within the last 12 months, OR ii). If on tamoxifen or toremifene within the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range, OR iii). In case of therapy induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal range per local normal range.
(3) Perimenopausal status is define as neither premenopausal nor postmenopausal Note: Throughout this document, perimenopausal and premenopausal status is grouped together and referred as "Premenopausal"
3. Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
4. Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an 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.
5. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2
6. Patient has adequate bone marrow and organ function as defined by ALL of the following laboratory values (as assessed by local laboratory):
(1) Absolute neutrophil count ≥ 1.5 × 10^9/L
(2) Platelets ≥ 100 × 10^9/L
(3) Hemoglobin ≥ 9.0 g/dL
(4) Potassium, sodium, calcium corrected for serum albumin and magnesium within normal limits or corrected to within normal limits with supplements before first dose of the study medication
(5) INR ≤1.5
(6) Serum creatinine <1.5 mg/dl or creatinine clearance≥50 mL/min
(7) In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be below 2.5 × ULN. If the patient has liver metastases, ALT and AST should be < 5 × ULN.
(8) Total serum bilirubin < ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in patients with well-documented Gilbert's Syndrome
7. Patient must have a 12-lead ECG with ALL of the following parameters at screening:
(1) QTcF interval at screening <450 msec (using Fridericia's correction)
(2) Resting heart rate ≥ 50 bpm
Exclusion Criteria
1. Patient who received any CDK4/6 inhibitor.
2. Patient who received any prior systemic hormonal therapy for advanced breast cancer; no more than one prior regimen of chemotherapy for the treatment of metastatic disease is permitted.
3. Patients who received (neo) adjuvant therapy for breast cancer are eligible. If the prior neo (adjuvant) therapy included letrozole or anastrozole the disease free interval must be greater than 12 months from the completion of treatment until study entry.
4. Patients who received ≤ 28 days of letrozole or anastrozole for advanced disease prior to inclusion in this trial are eligible.
5. Any prior (neo) adjuvant anti-cancer therapy or prior chemotherapy for metastatic disease must be stopped at least 5 half-lives or 7 days, whichever is longer, before study inclusion.
6. Patient is concurrently using other anti-cancer therapy.
2. Patient who received any prior systemic hormonal therapy for advanced breast cancer; no more than one prior regimen of chemotherapy for the treatment of metastatic disease is permitted.
3. Patients who received (neo) adjuvant therapy for breast cancer are eligible. If the prior neo (adjuvant) therapy included letrozole or anastrozole the disease free interval must be greater than 12 months from the completion of treatment until study entry.
4. Patients who received ≤ 28 days of letrozole or anastrozole for advanced disease prior to inclusion in this trial are eligible.
5. Any prior (neo) adjuvant anti-cancer therapy or prior chemotherapy for metastatic disease must be stopped at least 5 half-lives or 7 days, whichever is longer, before study inclusion.
6. Patient is concurrently using other anti-cancer therapy.
The Estimated Number of Participants
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Taiwan
20 participants
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Global
3000 participants
