Trial Outcomes & Findings for Pharmacokinetics and Pharmacogenomics of Ribociclib in Race-based Cohorts (NCT NCT04657679)
NCT ID: NCT04657679
Last Updated: 2024-11-26
Results Overview
Compare the exposure (i.e., AUC) of ribociclib at steady-state between CYP3A5 poor metabolizers (PM) and CYP3A5 intermediate or normal metabolizers (IM/NM) in each independent race-based cohort of women with advance breast cancer
Recruitment status
TERMINATED
Study phase
PHASE4
Target enrollment
21 participants
Primary outcome timeframe
On day 8-16 of cycle 1 (each cycle is 28 days)
Results posted on
2024-11-26
Participant Flow
Participant milestones
| Measure |
African American/Black
Subject who self identify as African American or Black with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
Non-Hispanic White
Subjects who self-identify as non-Hispanic White with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
|---|---|---|
|
Overall Study
STARTED
|
17
|
4
|
|
Overall Study
COMPLETED
|
14
|
3
|
|
Overall Study
NOT COMPLETED
|
3
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetics and Pharmacogenomics of Ribociclib in Race-based Cohorts
Baseline characteristics by cohort
| Measure |
African American/Black
n=17 Participants
Subject who self identify as African American or Black with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
Non-Hispanic White
n=4 Participants
Subjects who self-identify as non-Hispanic White with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
Total
n=21 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
11 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
17 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
17 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
CYP3A5 phenotype
IM/NM: intermediate metabolizers/normal metabolizers
|
9 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
CYP3A5 phenotype
PM: poor metabolizers
|
8 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: On day 8-16 of cycle 1 (each cycle is 28 days)Population: One subject in the Non-Hispanic white arm was excluded to prohibited medication. All Non-Hispanic white participants were in the CYP3A5 Poor Metabolizers (PM) group.
Compare the exposure (i.e., AUC) of ribociclib at steady-state between CYP3A5 poor metabolizers (PM) and CYP3A5 intermediate or normal metabolizers (IM/NM) in each independent race-based cohort of women with advance breast cancer
Outcome measures
| Measure |
African American/Black
n=14 Participants
Subject who self identify as African American or Black with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
Non-Hispanic White
n=3 Participants
Subjects who self-identify as non-Hispanic White with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
|---|---|---|
|
Ribociclib Area-under-the-curve (AUC)
CYP3A5 IM/NM
|
43546 hr*ng/mL
Interval 35298.0 to 46647.0
|
—
|
|
Ribociclib Area-under-the-curve (AUC)
CYP3A5 PM
|
39230 hr*ng/mL
Interval 18745.0 to 57566.0
|
33230 hr*ng/mL
Interval 17142.0 to 39492.0
|
SECONDARY outcome
Timeframe: On day 8-16 of cycle 1 (each cycle is 28 days)Population: One subject in the Non-Hispanic white arm was excluded to prohibited medication. All Non-Hispanic white participants were in the CYP3A5 Poor Metabolizers (PM) group.
Maximum concentration (Cmax) at steady state between different CYP3A5 phenotypes
Outcome measures
| Measure |
African American/Black
n=14 Participants
Subject who self identify as African American or Black with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
Non-Hispanic White
n=3 Participants
Subjects who self-identify as non-Hispanic White with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
|---|---|---|
|
Ribociclib Pharmacokinetic Properties - Maximum Concentration (Cmax)
Cmax CYP3A5 IM/NM
|
3140 ng/mL
Interval 1980.0 to 3540.0
|
—
|
|
Ribociclib Pharmacokinetic Properties - Maximum Concentration (Cmax)
Cmax CYP3A5 PM
|
3020 ng/mL
Interval 1300.0 to 3470.0
|
2300 ng/mL
Interval 2220.0 to 2640.0
|
SECONDARY outcome
Timeframe: On day 8-16 of cycle 1 (each cycle is 28 days)Population: One subject in the Non-Hispanic white arm was excluded to prohibited medication. All Non-Hispanic white participants were in the CYP3A5 Poor Metabolizers (PM) group.
the time to reach Cmax (Tmax) at steady state between different CYP3A5 phenotypes
Outcome measures
| Measure |
African American/Black
n=14 Participants
Subject who self identify as African American or Black with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
Non-Hispanic White
n=3 Participants
Subjects who self-identify as non-Hispanic White with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
|---|---|---|
|
Ribociclib Pharmacokinetic Properties - the Time to Reach Cmax (Tmax)
CYP3A5 IM/NM
|
2.0 hour
Interval 2.0 to 4.0
|
—
|
|
Ribociclib Pharmacokinetic Properties - the Time to Reach Cmax (Tmax)
CYP3A5 PM
|
3.8 hour
Interval 2.0 to 5.9
|
0.97 hour
Interval 0.58 to 4.1
|
SECONDARY outcome
Timeframe: On day 8-16 of cycle 1 (each cycle is 28 days)Population: One subject in the Non-Hispanic white arm was excluded to prohibited medication. All Non-Hispanic white participants were in the CYP3A5 Poor Metabolizers (PM) group.
clearance at steady state between different CYP3A5 phenotypes
Outcome measures
| Measure |
African American/Black
n=14 Participants
Subject who self identify as African American or Black with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
Non-Hispanic White
n=3 Participants
Subjects who self-identify as non-Hispanic White with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
|---|---|---|
|
Ribociclib Pharmacokinetic Properties - Clearance
CYP3A5 IM/NM
|
13.78 liter/hour
Interval 12.86 to 17.0
|
—
|
|
Ribociclib Pharmacokinetic Properties - Clearance
CYP3A5 PM
|
15.29 liter/hour
Interval 10.42 to 32.0
|
18.06 liter/hour
Interval 15.19 to 35.0
|
SECONDARY outcome
Timeframe: days 8-16 of cycle 1 (28 day cycle)Population: One subject in the Non-Hispanic white arm was excluded due to prohibited medication.
Volume of distribution(vd) at steady state between different CYP3A5 phenotypes
Outcome measures
| Measure |
African American/Black
n=14 Participants
Subject who self identify as African American or Black with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
Non-Hispanic White
n=3 Participants
Subjects who self-identify as non-Hispanic White with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
|---|---|---|
|
Ribociclib Pharmacokinetic Properties - Volume of Distribution(vd)
CYP3A5 IM/NM
|
413.88 Liters
Interval 370.75 to 520.77
|
—
|
|
Ribociclib Pharmacokinetic Properties - Volume of Distribution(vd)
CYP3A5 PM
|
465.33 Liters
Interval 319.72 to 813.19
|
455.90 Liters
Interval 438.76 to 954.99
|
SECONDARY outcome
Timeframe: On day 8-16 of cycle 1 (each cycle is 28 days)Population: One subject in the Non-Hispanic white arm was excluded to prohibited medication. All Non-Hispanic white participants were in the CYP3A5 Poor Metabolizers (PM) group.
Elimination half-life (t1/2) at steady state between different CYP3A5 phenotypes
Outcome measures
| Measure |
African American/Black
n=14 Participants
Subject who self identify as African American or Black with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
Non-Hispanic White
n=3 Participants
Subjects who self-identify as non-Hispanic White with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
|---|---|---|
|
Ribociclib Pharmacokinetic Properties - Elimination Half-life
CYP3A5 IM/NM
|
21.24 hour
Interval 20.61 to 25.12
|
—
|
|
Ribociclib Pharmacokinetic Properties - Elimination Half-life
CYP3A5 PM
|
21.26 hour
Interval 21.09 to 22.7
|
18.91 hour
Interval 17.5 to 20.02
|
SECONDARY outcome
Timeframe: Baseline, day 8-16 of cycle 1 and prior to cycle 2 (each cycle is 28 days)Population: One subject in the Non-Hispanic white arm was excluded to prohibited medication.
Change in QTc interval between 1) baseline and between days 8-16 of cycle 1 (midcycle), and 2) baseline and scheduled visit prior to initiation of cycle 2 (C2), between different CYP3A5 phenotypes.
Outcome measures
| Measure |
African American/Black
n=14 Participants
Subject who self identify as African American or Black with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
Non-Hispanic White
n=3 Participants
Subjects who self-identify as non-Hispanic White with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
|---|---|---|
|
Change in QTc Interval
MidCycle -CYP3A5 IM/NM
|
19 Change in ms
Interval 0.0 to 37.0
|
—
|
|
Change in QTc Interval
MidCycle- CYP3A5 PM
|
-7 Change in ms
Interval -11.0 to 16.0
|
23 Change in ms
Interval 23.0 to 36.0
|
|
Change in QTc Interval
Prior to C2- CYP3A5 IM/NM
|
11 Change in ms
Interval -26.0 to 29.0
|
—
|
|
Change in QTc Interval
Prior to C2- CYP3A5 PM
|
-4 Change in ms
Interval -17.0 to 5.0
|
31 Change in ms
Interval 23.0 to 40.0
|
SECONDARY outcome
Timeframe: from baseilne through prior to cycle 2 (each cycle is 28 days)Population: One subject in the Non-Hispanic white arm was excluded to prohibited medication.
Occurrence of neutropenia
Outcome measures
| Measure |
African American/Black
n=14 Participants
Subject who self identify as African American or Black with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
Non-Hispanic White
n=3 Participants
Subjects who self-identify as non-Hispanic White with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
|---|---|---|
|
Laboratory Abnormalities - Neutropenia
CYP3A5 IM/NM
|
0 Participants
|
—
|
|
Laboratory Abnormalities - Neutropenia
CYP3A5 PM
|
3 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: From Baseline through prior to cycle 2 (each cycle is 28 days)Population: One subject in the Non-Hispanic white arm was excluded to prohibited medication.
Occurrence of Laboratory abnormalities: AST
Outcome measures
| Measure |
African American/Black
n=14 Participants
Subject who self identify as African American or Black with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
Non-Hispanic White
n=3 Participants
Subjects who self-identify as non-Hispanic White with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
|---|---|---|
|
Laboratory Abnormalities - Aspartate Aminotransferase (AST)
CYP3A5 IM/NM
|
0 Participants
|
—
|
|
Laboratory Abnormalities - Aspartate Aminotransferase (AST)
CYP3A5 PM
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From Baseline to prior to cycle 2 (each cycle is 28 days)Population: One subject in the Non-Hispanic white arm was excluded to prohibited medication.
Occurrence of Laboratory abnormalities: ALT between between different CYP3A5 phenotypes.
Outcome measures
| Measure |
African American/Black
n=14 Participants
Subject who self identify as African American or Black with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
Non-Hispanic White
n=3 Participants
Subjects who self-identify as non-Hispanic White with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
|---|---|---|
|
Laboratory Abnormalities -Alanine Aminotransferase (ALT)
CYP3A5 IM/NM
|
1 Participants
|
—
|
|
Laboratory Abnormalities -Alanine Aminotransferase (ALT)
CYP3A5 PM
|
1 Participants
|
0 Participants
|
Adverse Events
African American/Black
Serious events: 2 serious events
Other events: 14 other events
Deaths: 0 deaths
Non-Hispanic White
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
African American/Black
n=14 participants at risk
Subject who self identify as African American or Black with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
Non-Hispanic White
n=3 participants at risk
Subjects who self-identify as non-Hispanic White with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
|---|---|---|
|
Investigations
Aspartate aminotransferase increased
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Investigations
Alanine aminotransferase increased
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Blood and lymphatic system disorders
White blood cell decreased
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Renal and urinary disorders
Acute kidney injury
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
Other adverse events
| Measure |
African American/Black
n=14 participants at risk
Subject who self identify as African American or Black with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
Non-Hispanic White
n=3 participants at risk
Subjects who self-identify as non-Hispanic White with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers)
Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
14.3%
2/14 • Number of events 2 • 29 days
|
0.00%
0/3 • 29 days
|
|
Blood and lymphatic system disorders
Neutrophil count decreased
|
28.6%
4/14 • Number of events 4 • 29 days
|
0.00%
0/3 • 29 days
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Blood and lymphatic system disorders
White blood cell decreased
|
28.6%
4/14 • Number of events 6 • 29 days
|
0.00%
0/3 • 29 days
|
|
Cardiac disorders
Palpitations
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Cardiac disorders
Sinus tachycardia
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Gastrointestinal disorders
Abdominal pain
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Gastrointestinal disorders
Constipation
|
14.3%
2/14 • Number of events 2 • 29 days
|
0.00%
0/3 • 29 days
|
|
Gastrointestinal disorders
Diarrhea
|
28.6%
4/14 • Number of events 5 • 29 days
|
33.3%
1/3 • Number of events 2 • 29 days
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, specify
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Gastrointestinal disorders
Mucositis oral
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Gastrointestinal disorders
Nausea
|
35.7%
5/14 • Number of events 7 • 29 days
|
66.7%
2/3 • Number of events 2 • 29 days
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/14 • 29 days
|
33.3%
1/3 • Number of events 1 • 29 days
|
|
Gastrointestinal disorders
Vomiting
|
28.6%
4/14 • Number of events 5 • 29 days
|
33.3%
1/3 • Number of events 1 • 29 days
|
|
General disorders
Edema limbs
|
14.3%
2/14 • Number of events 2 • 29 days
|
0.00%
0/3 • 29 days
|
|
General disorders
Fatigue
|
14.3%
2/14 • Number of events 3 • 29 days
|
0.00%
0/3 • 29 days
|
|
Infections and infestations
Gum infection
|
0.00%
0/14 • 29 days
|
33.3%
1/3 • Number of events 1 • 29 days
|
|
Infections and infestations
Infections and infestations - Other, specify
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Metabolism and nutrition disorders
Anorexia
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
14.3%
2/14 • Number of events 2 • 29 days
|
33.3%
1/3 • Number of events 1 • 29 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Musculoskeletal and connective tissue disorders
Bone Pain
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Nervous system disorders
Headache
|
14.3%
2/14 • Number of events 2 • 29 days
|
33.3%
1/3 • Number of events 2 • 29 days
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
0.00%
0/14 • 29 days
|
33.3%
1/3 • Number of events 1 • 29 days
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
7.1%
1/14 • Number of events 1 • 29 days
|
33.3%
1/3 • Number of events 2 • 29 days
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
14.3%
2/14 • Number of events 3 • 29 days
|
0.00%
0/3 • 29 days
|
|
Vascular disorders
Hot flashes
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Vascular disorders
Hypotension
|
7.1%
1/14 • Number of events 1 • 29 days
|
0.00%
0/3 • 29 days
|
|
Cardiac disorders
QTc Prolongation
|
35.7%
5/14 • Number of events 5 • 29 days
|
66.7%
2/3 • Number of events 2 • 29 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place