Brief Summary
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
Brief Title
Adjuvant Ribociclib With Endocrine Therapy in Hormone Receptor+/HER2- 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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Breast Cancer
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.
* 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.
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
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
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03078751
Org Class
Industry
Org Full Name
Novartis
Org Study Id
CLEE011G2301
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome 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
Outcome Measure
Number of Participants With Adverse Events and Serious Adverse Events
Outcome Time Frame
Up to 26 months
Outcome Description
These are the percentage of participants that had adverse events or serious adverse events regardless of whether is was suspected to be drug-related or not
Outcome Measure
Percentage of Participants With Adverse Events and Serious Adverse Events
Outcome Time Frame
Up to 26 months
Secondary Ids
Secondary Id
2014-001795-53
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Della Makower
Investigator Email
DMAKOWER@montefiore.org
Investigator Phone