Trial Outcomes & Findings for LEE011 (Ribociclib) in Combination With Docetaxel Plus Prednisone in mCRPC (NCT NCT02494921)
NCT ID: NCT02494921
Last Updated: 2022-08-31
Results Overview
Maximally tolerated dose (MTD) of ribociclib in combination with docetaxel and prednisone is based upon evaluation of dose-limiting toxicities (DLTs) and adverse events for all participants who received treatment in Phase Ib. If 1 of 3 participants in a cohort experiences a DLT, then the cohort will be expanded to treat an additional 3 participants. If only 1 of 6 participants experiences a DLT, the next cohort of participants will be treated at the next higher dose level. If 2 or more participants in a cohort experience a DLT, then MTD has been exceeded and the previous dose level will be considered the MTD. If more than 1 of 6 patients experience a DLT at dose level IA then the study will be terminated, as the MTD cannot be determined and de-escalation from dose level IA is not planned. Per Investigator discretion the Recommended Phase 2 Dose (RP2D) schedule of ribociclib and docetaxel may be established in the absence of reaching MTD.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
43 participants
Primary outcome timeframe
Up to 2 years
Results posted on
2022-08-31
Participant Flow
The initial dosing schedule was chosen as the most efficacious dosing schedule of docetaxel. If dose level I is not tolerated, then alternative dosing schedules of docetaxel were evaluated, starting with dose level IA. Depending on the safety data observed, alternative dosing schedules and intermediate dose levels of ribociclib was investigated (Cohort / Dose Levels IC - IIIC) per protocol.
Participant milestones
| Measure |
Treatment (Phase 1b, Non-RP2D, Cohort I)
The starting cohort dose level (1) for docetaxel will be 75 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, Non-RP2D, Cohort IA)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, Non-RP2D, Cohort IIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 300 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, R2PD, Cohort IIIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 2, RP2D)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
|---|---|---|---|---|---|
|
Phase 1b, Dose Level I
STARTED
|
5
|
0
|
0
|
0
|
0
|
|
Phase 1b, Dose Level I
COMPLETED
|
3
|
0
|
0
|
0
|
0
|
|
Phase 1b, Dose Level I
NOT COMPLETED
|
2
|
0
|
0
|
0
|
0
|
|
Phase 1b, Dose Level IA
STARTED
|
0
|
4
|
0
|
0
|
0
|
|
Phase 1b, Dose Level IA
COMPLETED
|
0
|
3
|
0
|
0
|
0
|
|
Phase 1b, Dose Level IA
NOT COMPLETED
|
0
|
1
|
0
|
0
|
0
|
|
Phase 1b, Dose Level IIC
STARTED
|
0
|
0
|
4
|
0
|
0
|
|
Phase 1b, Dose Level IIC
COMPLETED
|
0
|
0
|
3
|
0
|
0
|
|
Phase 1b, Dose Level IIC
NOT COMPLETED
|
0
|
0
|
1
|
0
|
0
|
|
Phase 1b, Dose Level IIIC, RP2D
STARTED
|
0
|
0
|
0
|
6
|
0
|
|
Phase 1b, Dose Level IIIC, RP2D
COMPLETED
|
0
|
0
|
0
|
6
|
0
|
|
Phase 1b, Dose Level IIIC, RP2D
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Phase 2, RP2D
STARTED
|
0
|
0
|
0
|
0
|
24
|
|
Phase 2, RP2D
COMPLETED
|
0
|
0
|
0
|
0
|
24
|
|
Phase 2, RP2D
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Treatment (Phase 1b, Non-RP2D, Cohort I)
The starting cohort dose level (1) for docetaxel will be 75 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, Non-RP2D, Cohort IA)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, Non-RP2D, Cohort IIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 300 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, R2PD, Cohort IIIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 2, RP2D)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
|---|---|---|---|---|---|
|
Phase 1b, Dose Level I
Adverse Event
|
2
|
0
|
0
|
0
|
0
|
|
Phase 1b, Dose Level IA
Adverse Event
|
0
|
1
|
0
|
0
|
0
|
|
Phase 1b, Dose Level IIC
Physician Decision
|
0
|
0
|
1
|
0
|
0
|
Baseline Characteristics
LEE011 (Ribociclib) in Combination With Docetaxel Plus Prednisone in mCRPC
Baseline characteristics by cohort
| Measure |
Treatment (Phase 1b, Non-RP2D, Cohort I)
n=5 Participants
The starting cohort dose level (1) for docetaxel will be 75 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle
|
Treatment (Phase 1b, Non-RP2D, Cohort IA)
n=4 Participants
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle
|
Treatment (Phase 1b, Non-RP2D, Cohort IIC)
n=4 Participants
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 300 mg orally once daily, starting on day 1 of the 21-day cycle
|
Treatment (Phase 1b, RP2D, Cohort IIIC)
n=6 Participants
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle
|
Treatment (Phase 2, RP2D)
n=24 Participants
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle
|
Total
n=43 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Customized
50-59 years
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
5 Participants
n=8 Participants
|
|
Age, Customized
60-69 years
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
20 Participants
n=8 Participants
|
|
Age, Customized
70-79 years
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
16 Participants
n=8 Participants
|
|
Age, Customized
80-89 years
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
24 Participants
n=21 Participants
|
43 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
4 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
22 Participants
n=21 Participants
|
37 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=8 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
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
19 Participants
n=21 Participants
|
35 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
4 Participants
n=8 Participants
|
|
Region of Enrollment
United States
|
5 participants
n=5 Participants
|
4 participants
n=7 Participants
|
4 participants
n=5 Participants
|
6 participants
n=4 Participants
|
24 participants
n=21 Participants
|
43 participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Up to 2 yearsPopulation: All participants in Phase 1b including those who received the RP2D were included in this analysis
Maximally tolerated dose (MTD) of ribociclib in combination with docetaxel and prednisone is based upon evaluation of dose-limiting toxicities (DLTs) and adverse events for all participants who received treatment in Phase Ib. If 1 of 3 participants in a cohort experiences a DLT, then the cohort will be expanded to treat an additional 3 participants. If only 1 of 6 participants experiences a DLT, the next cohort of participants will be treated at the next higher dose level. If 2 or more participants in a cohort experience a DLT, then MTD has been exceeded and the previous dose level will be considered the MTD. If more than 1 of 6 patients experience a DLT at dose level IA then the study will be terminated, as the MTD cannot be determined and de-escalation from dose level IA is not planned. Per Investigator discretion the Recommended Phase 2 Dose (RP2D) schedule of ribociclib and docetaxel may be established in the absence of reaching MTD.
Outcome measures
| Measure |
Treatment (Phase 1b)
n=19 Participants
The starting cohort dose level (I) for docetaxel will be 75 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle. If dose level (1) is not tolerated, then alternative dosing schedules of docetaxel will be evaluated, starting with dose level IA of 60mg/m2 docetaxel.
|
Treatment (Phase 1b, Non-RP2D, Cohort IA)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, Non-RP2D, Cohort IIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 300 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, R2PD, Cohort IIIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 2, RP2D)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
|---|---|---|---|---|---|
|
Maximally Tolerated Dose (MTD) (Phase 1b)
|
NA mg/m^2
MTD was not reached
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to 2 yearsPopulation: All participants in Phase 1b, including those who received the Recommended Phase 2 Dose for docetaxel and ribociclib will be included in the analysis. The final RP2D was determined to be 60mg/m\^2 of docetaxel in combination with 400mg of ribociclib.
The RP2D of docetaxel will be reported when used in combination with ribociclib and prednisone based upon evaluation of dose-limiting toxicities (DLTs) and adverse events for all participants in the Phase Ib group. Per Investigator discretion, the RP2D schedule of docetaxel and ribociclib may be established in the absence of reaching MTD, based on the cumulative safety data of the treatment regimen.
Outcome measures
| Measure |
Treatment (Phase 1b)
n=19 Participants
The starting cohort dose level (I) for docetaxel will be 75 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle. If dose level (1) is not tolerated, then alternative dosing schedules of docetaxel will be evaluated, starting with dose level IA of 60mg/m2 docetaxel.
|
Treatment (Phase 1b, Non-RP2D, Cohort IA)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, Non-RP2D, Cohort IIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 300 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, R2PD, Cohort IIIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 2, RP2D)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
|---|---|---|---|---|---|
|
RP2D of Docetaxel (Phase 1b)
|
60 mg/m^2
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to 6 monthsPopulation: All participants in Phase 1b (N=6) and Phase 2 (N=24) who received the RP2D were included in the analysis.
Radiographic progression-free survival will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The percent of participants has been estimated using the Kaplan-Meier product limit method. Duration will be measured from day 1 of study treatment to first date of radiographic progression or death, whichever occurs first, for all Phase 1b or Phase 2 participants receiving the RP2D. Participants who discontinue study therapy for toxicity, withdrawal from study, or prostate-specific antigen (PSA)-only progression, will be censored at the date of last radiographic tumor assessment for this analysis. Patients who discontinue therapy for evidence of clinical progression/clinical deterioration will be included in this analysis.
Outcome measures
| Measure |
Treatment (Phase 1b)
n=30 Participants
The starting cohort dose level (I) for docetaxel will be 75 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle. If dose level (1) is not tolerated, then alternative dosing schedules of docetaxel will be evaluated, starting with dose level IA of 60mg/m2 docetaxel.
|
Treatment (Phase 1b, Non-RP2D, Cohort IA)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, Non-RP2D, Cohort IIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 300 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, R2PD, Cohort IIIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 2, RP2D)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
|---|---|---|---|---|---|
|
Percentage of Participants With Radiographic Progression-free Survival at 6 Months (Phase 1b/2 RP2D)
|
65.8 percentage of participants
Interval 50.6 to 85.5
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: All participants in Phase 1b (N=6) and Phase 2 (N=24) who received the RP2D were included in the analysis.
Radiographic progression-free survival will be assessed using RECIST version 1.1. Median duration will be Estimated using the Kaplan-Meier product limit method. Duration will be measured from day 1 of study treatment to first date of radiographic progression or death, whichever occurs sooner for participants in Phase 1b and Phase 2 who receive the RP2D. Participants who discontinue study therapy for toxicity, withdrawal from study, or prostate-specific antigen (PSA)-only progression, will be censored at the date of last radiographic tumor assessment for this analysis. Participants who discontinue therapy for evidence of clinical progression/clinical deterioration will be included in this analysis.
Outcome measures
| Measure |
Treatment (Phase 1b)
n=30 Participants
The starting cohort dose level (I) for docetaxel will be 75 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle. If dose level (1) is not tolerated, then alternative dosing schedules of docetaxel will be evaluated, starting with dose level IA of 60mg/m2 docetaxel.
|
Treatment (Phase 1b, Non-RP2D, Cohort IA)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, Non-RP2D, Cohort IIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 300 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, R2PD, Cohort IIIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 2, RP2D)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
|---|---|---|---|---|---|
|
Median Radiographic Progression-free Survival (Phase1b/2 RP2D)
|
8.09 months
Interval 6.89 to 10.03
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: Of 30 possible participants, only 13 met the criteria of both measurable disease at baseline and at least one restaging scan on treatment.
ORR will be assessed using RECIST version 1.1 criteria, and defined as participants who were determined to have demonstrated a complete response (CR) and/or partial response (PR). Participants must have measurable disease at baseline with at least one restaging scan on treatment to be included in the analysis.
Outcome measures
| Measure |
Treatment (Phase 1b)
n=13 Participants
The starting cohort dose level (I) for docetaxel will be 75 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle. If dose level (1) is not tolerated, then alternative dosing schedules of docetaxel will be evaluated, starting with dose level IA of 60mg/m2 docetaxel.
|
Treatment (Phase 1b, Non-RP2D, Cohort IA)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, Non-RP2D, Cohort IIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 300 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, R2PD, Cohort IIIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 2, RP2D)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
|---|---|---|---|---|---|
|
Objective Response Rate (ORR) (Phase1b/2 RP2D)
|
23.1 percentage of participants
Interval 9.1 to 61.4
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: Of 30 possible participants, only 13 met the criteria of both measurable disease at baseline and at least one restaging scan on treatment.
For participants with both measurable disease at baseline and at least one restaging scan on treatment, duration of response will be defined as the time criteria are met for CR or PR until recurrent or progressive disease is objectively documented.
Outcome measures
| Measure |
Treatment (Phase 1b)
n=13 Participants
The starting cohort dose level (I) for docetaxel will be 75 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle. If dose level (1) is not tolerated, then alternative dosing schedules of docetaxel will be evaluated, starting with dose level IA of 60mg/m2 docetaxel.
|
Treatment (Phase 1b, Non-RP2D, Cohort IA)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, Non-RP2D, Cohort IIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 300 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, R2PD, Cohort IIIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 2, RP2D)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
|---|---|---|---|---|---|
|
Median Duration of Response (Phase1b/2 RP2D)
|
141.5 days
Interval 59.0 to 259.0
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: Of 30 possible participants, 5 participants did not have documented PSA response values available and were excluded from the analysis
PSA progression occurs when the PSA value has increased 25% or greater above nadir and an absolute increase of 2 ng/mL or more from the nadir is documented. Where no decline is observed, PSA progression similarly occurs when a 25% increase from baseline value along with an increase in absolute value of 2 ng/mL or more per the Prostate Cancer Working Group 2 (PCWG2) Criteria.
Outcome measures
| Measure |
Treatment (Phase 1b)
n=25 Participants
The starting cohort dose level (I) for docetaxel will be 75 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle. If dose level (1) is not tolerated, then alternative dosing schedules of docetaxel will be evaluated, starting with dose level IA of 60mg/m2 docetaxel.
|
Treatment (Phase 1b, Non-RP2D, Cohort IA)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, Non-RP2D, Cohort IIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 300 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, R2PD, Cohort IIIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 2, RP2D)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
|---|---|---|---|---|---|
|
Prostate-Specific Antigen (PSA) Response Rate (Phase 1b/2 RP2D)
|
32 percentage of participants
Interval 15.0 to 53.5
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: Of 30 possible participants, 8 participants were excluded from the analysis due to lack of documented PSA after baseline
The PSA response duration commences on the date of the first 50% decline in PSA. The response duration ends when the PSA value increases by 25% above the nadir, provided that the increase in the absolute-value PSA level is at least 5 ng/mL or back to baseline, whichever is lower. The probability distribution of the median time to PSA progression will be estimated using the Kaplan-Meier product limit method.
Outcome measures
| Measure |
Treatment (Phase 1b)
n=22 Participants
The starting cohort dose level (I) for docetaxel will be 75 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle. If dose level (1) is not tolerated, then alternative dosing schedules of docetaxel will be evaluated, starting with dose level IA of 60mg/m2 docetaxel.
|
Treatment (Phase 1b, Non-RP2D, Cohort IA)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, Non-RP2D, Cohort IIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 300 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, R2PD, Cohort IIIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 2, RP2D)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
|---|---|---|---|---|---|
|
Median PSA Progression-Free Survival (Phase 1b/2 RP2D)
|
7.15 months
Interval 2.86 to 8.45
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsThe number of participants with reported adverse events related to the treatment regimen will be descriptively reported using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Analyses will be performed for all patients having received at least one dose of study drug.
Outcome measures
| Measure |
Treatment (Phase 1b)
n=5 Participants
The starting cohort dose level (I) for docetaxel will be 75 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle. If dose level (1) is not tolerated, then alternative dosing schedules of docetaxel will be evaluated, starting with dose level IA of 60mg/m2 docetaxel.
|
Treatment (Phase 1b, Non-RP2D, Cohort IA)
n=4 Participants
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, Non-RP2D, Cohort IIC)
n=4 Participants
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 300 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, R2PD, Cohort IIIC)
n=6 Participants
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 2, RP2D)
n=24 Participants
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
|---|---|---|---|---|---|
|
Number of Participants With Treatment-Related Adverse Events
|
5 Participants
|
4 Participants
|
4 Participants
|
6 Participants
|
22 Participants
|
SECONDARY outcome
Timeframe: Pre-dose on day 1, and 1, 2, 4, and 24 hours post-dosePopulation: All participants in Phase 1b, Non-RP2D were grouped for this analysis since the drug of interest is ribociclib only. All participants in the combined Phase 1b, non-RP2D group did not receive the 400 mg dose at any time, and 1 participant did not have serum levels recorded. Participants in the combined Phase 1b, RP2D cohort did not receive \< 400 mg dose at any time.
The estimated AUC for serum concentration of ribociclib for a 24 hour interval after dose will be reported using descriptive statistics for all participants in Phase 1b who received at least one dose of study treatment and completed a serum blood draw.
Outcome measures
| Measure |
Treatment (Phase 1b)
n=12 Participants
The starting cohort dose level (I) for docetaxel will be 75 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle. If dose level (1) is not tolerated, then alternative dosing schedules of docetaxel will be evaluated, starting with dose level IA of 60mg/m2 docetaxel.
|
Treatment (Phase 1b, Non-RP2D, Cohort IA)
n=6 Participants
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, Non-RP2D, Cohort IIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 300 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, R2PD, Cohort IIIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 2, RP2D)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
|---|---|---|---|---|---|
|
Mean Area Under Curve (AUC) 0-24 Hour (Phase 1b)
200 mg ribociclib
|
2909 ng*hrs/mL
Interval 1699.7 to 4119.2
|
—
|
—
|
—
|
—
|
|
Mean Area Under Curve (AUC) 0-24 Hour (Phase 1b)
300 mg ribociclib
|
3340.3 ng*hrs/mL
Interval 1825.3 to 6491.1
|
—
|
—
|
—
|
—
|
|
Mean Area Under Curve (AUC) 0-24 Hour (Phase 1b)
400 mg ribociclib
|
—
|
6531.6 ng*hrs/mL
Interval 2922.5 to 10140.6
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose on day 1, and 1, 2, 4, and 24 hours post-dosePopulation: All participants in Phase 1b, Non-RP2D were grouped for this analysis since the drug of interest is ribociclib only. All participants in the combined Phase 1b, non-RP2D group did not receive the 400 mg dose at any time, and 1 participant did not have serum levels recorded. Participants in the combined Phase 1b, RP2D cohort did not receive \< 400 mg dose at any time.
The maximum concentration (Cmax) is shown to reflect not only the rate but also the extent of absorption. The mean Cmax for serum concentration of ribociclib will be reported using descriptive statistics for all participants in Phase 1b who received at least one dose of study treatment and completed a serum blood draw.
Outcome measures
| Measure |
Treatment (Phase 1b)
n=12 Participants
The starting cohort dose level (I) for docetaxel will be 75 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle. If dose level (1) is not tolerated, then alternative dosing schedules of docetaxel will be evaluated, starting with dose level IA of 60mg/m2 docetaxel.
|
Treatment (Phase 1b, Non-RP2D, Cohort IA)
n=6 Participants
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, Non-RP2D, Cohort IIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 300 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, R2PD, Cohort IIIC)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 2, RP2D)
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
|---|---|---|---|---|---|
|
Mean Maximum Serum Concentration of Ribociclib (Cmax) (Phase 1b)
300 mg Ribociclib
|
289.8 ng/mL
Interval 92.5 to 672.0
|
—
|
—
|
—
|
—
|
|
Mean Maximum Serum Concentration of Ribociclib (Cmax) (Phase 1b)
200 mg Ribociclib
|
207.5 ng/mL
Interval 135.4 to 279.6
|
—
|
—
|
—
|
—
|
|
Mean Maximum Serum Concentration of Ribociclib (Cmax) (Phase 1b)
400 mg Ribociclib
|
—
|
393.6 ng/mL
Interval 139.5 to 647.6
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: An intermittent ribociclib dosing scheduled was pursued so a steady-state serum concentration level could not be determined.
Steady-state serum concentration occurs when the amount of a drug being absorbed is the same amount that is being cleared from the body when the drug is given continuously. Steady-state concentration is the time during which the concentration of the drug in the body stays consistent. The estimated steady state for serum concentration of ribociclib will be reported using descriptive statistics for all participants in Phase 1b who received a steady dosing schedule of study treatment and completed a serum blood draw.
Outcome measures
Outcome data not reported
Adverse Events
Treatment (Phase 1b, Non-RP2D, Cohort I)
Serious events: 4 serious events
Other events: 5 other events
Deaths: 4 deaths
Treatment (Phase 1b, Non-RP2D, Cohort IA)
Serious events: 2 serious events
Other events: 4 other events
Deaths: 1 deaths
Treatment (Phase 1b, Non-RP2D, Cohort IIC)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 3 deaths
Treatment (Phase 1b, RP2D, Cohort IIIC)
Serious events: 3 serious events
Other events: 6 other events
Deaths: 3 deaths
Treatment (Phase 2, RP2D)
Serious events: 5 serious events
Other events: 22 other events
Deaths: 11 deaths
Serious adverse events
| Measure |
Treatment (Phase 1b, Non-RP2D, Cohort I)
n=5 participants at risk
The starting cohort dose level (1) for docetaxel will be 75 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, Non-RP2D, Cohort IA)
n=4 participants at risk
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, Non-RP2D, Cohort IIC)
n=4 participants at risk
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 300 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, RP2D, Cohort IIIC)
n=6 participants at risk
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 2, RP2D)
n=24 participants at risk
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
|---|---|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
20.0%
1/5 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Cardiac disorders
Cardiac Arrest
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
4.2%
1/24 • Number of events 1 • Up to 2 years
|
|
General disorders
Fatigue
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
4.2%
1/24 • Number of events 1 • Up to 2 years
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
40.0%
2/5 • Number of events 2 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Nervous system disorders
Intracranial hemorrhage
|
20.0%
1/5 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Nervous system disorders
Seizure
|
20.0%
1/5 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Nervous system disorders
Headache
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Vascular disorders
Thromboembolic event
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
33.3%
2/6 • Number of events 2 • Up to 2 years
|
4.2%
1/24 • Number of events 1 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
4.2%
1/24 • Number of events 1 • Up to 2 years
|
|
Eye disorders
Right lower visual field cut
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Nervous system disorders
Transient ischemic attacks
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Surgical and medical procedures
Aortic valve replacement
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
4.2%
1/24 • Number of events 1 • Up to 2 years
|
|
General disorders
Pain
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
4.2%
1/24 • Number of events 1 • Up to 2 years
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
4.2%
1/24 • Number of events 1 • Up to 2 years
|
|
Infections and infestations
Lung infection
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
4.2%
1/24 • Number of events 1 • Up to 2 years
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
4.2%
1/24 • Number of events 1 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
4.2%
1/24 • Number of events 1 • Up to 2 years
|
Other adverse events
| Measure |
Treatment (Phase 1b, Non-RP2D, Cohort I)
n=5 participants at risk
The starting cohort dose level (1) for docetaxel will be 75 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, Non-RP2D, Cohort IA)
n=4 participants at risk
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, Non-RP2D, Cohort IIC)
n=4 participants at risk
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 300 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 1b, RP2D, Cohort IIIC)
n=6 participants at risk
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
Treatment (Phase 2, RP2D)
n=24 participants at risk
The starting cohort dose level (1) for docetaxel will be 60 mg/m\^2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 400 mg orally once daily, starting on day 1 of the 21-day cycle.
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/5 • Up to 2 years
|
50.0%
2/4 • Number of events 4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
50.0%
3/6 • Number of events 5 • Up to 2 years
|
20.8%
5/24 • Number of events 8 • Up to 2 years
|
|
Blood and lymphatic system disorders
Hypoprotenemia
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Blood and lymphatic system disorders
Orthostatic Hypertension
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Cardiac disorders
Chest pain - cardiac
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Cardiac disorders
Chest Pressure
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Cardiac disorders
Palpitations
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Cardiac disorders
Palpitations (intermittent)
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Eye disorders
Epiphoria
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
8.3%
2/24 • Number of events 2 • Up to 2 years
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Gastrointestinal disorders
Abdominal pain
|
40.0%
2/5 • Number of events 2 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
4.2%
1/24 • Number of events 1 • Up to 2 years
|
|
Gastrointestinal disorders
Constipation
|
20.0%
1/5 • Number of events 2 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
12.5%
3/24 • Number of events 3 • Up to 2 years
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
33.3%
2/6 • Number of events 3 • Up to 2 years
|
29.2%
7/24 • Number of events 9 • Up to 2 years
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
8.3%
2/24 • Number of events 2 • Up to 2 years
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
8.3%
2/24 • Number of events 2 • Up to 2 years
|
|
Gastrointestinal disorders
Emesis
|
20.0%
1/5 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Gastrointestinal disorders
Mucositis oral
|
60.0%
3/5 • Number of events 3 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
33.3%
2/6 • Number of events 3 • Up to 2 years
|
12.5%
3/24 • Number of events 4 • Up to 2 years
|
|
Gastrointestinal disorders
Nausea
|
40.0%
2/5 • Number of events 2 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
50.0%
2/4 • Number of events 2 • Up to 2 years
|
83.3%
5/6 • Number of events 6 • Up to 2 years
|
41.7%
10/24 • Number of events 19 • Up to 2 years
|
|
General disorders
Bilateral hip pain
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
General disorders
Bilateral posterior rib pain
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
General disorders
Bone and hand discomfort
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
General disorders
Edema Limbs
|
20.0%
1/5 • Number of events 1 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
33.3%
2/6 • Number of events 2 • Up to 2 years
|
16.7%
4/24 • Number of events 7 • Up to 2 years
|
|
General disorders
Fatigue
|
60.0%
3/5 • Number of events 3 • Up to 2 years
|
75.0%
3/4 • Number of events 3 • Up to 2 years
|
50.0%
2/4 • Number of events 3 • Up to 2 years
|
83.3%
5/6 • Number of events 11 • Up to 2 years
|
58.3%
14/24 • Number of events 20 • Up to 2 years
|
|
General disorders
Fever
|
40.0%
2/5 • Number of events 2 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
8.3%
2/24 • Number of events 3 • Up to 2 years
|
|
General disorders
Infusion related reaction
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
8.3%
2/24 • Number of events 2 • Up to 2 years
|
|
General disorders
Injection site reaction
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
General disorders
Left anterolateral rib pain
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
General disorders
Left pubic rami pain
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
General disorders
Localized edema
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
8.3%
2/24 • Number of events 3 • Up to 2 years
|
|
General disorders
Neck edema
|
20.0%
1/5 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
General disorders
Non-cardiac chest pain
|
20.0%
1/5 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
8.3%
2/24 • Number of events 3 • Up to 2 years
|
|
General disorders
Sleep disturbances
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Infections and infestations
Sinusitis
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Infections and infestations
Upper respiratory infection
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
33.3%
2/6 • Number of events 2 • Up to 2 years
|
8.3%
2/24 • Number of events 3 • Up to 2 years
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
8.3%
2/24 • Number of events 2 • Up to 2 years
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
8.3%
2/24 • Number of events 2 • Up to 2 years
|
|
Investigations
Alkaline phosphatase increased
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
4.2%
1/24 • Number of events 3 • Up to 2 years
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 3 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
8.3%
2/24 • Number of events 2 • Up to 2 years
|
|
Investigations
Creatinine increased
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 2 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
16.7%
1/6 • Number of events 6 • Up to 2 years
|
4.2%
1/24 • Number of events 1 • Up to 2 years
|
|
Investigations
International Normalized Ratio (INR) increased
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
12.5%
3/24 • Number of events 12 • Up to 2 years
|
|
Investigations
Neutrophil count decreased
|
80.0%
4/5 • Number of events 16 • Up to 2 years
|
75.0%
3/4 • Number of events 7 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
50.0%
3/6 • Number of events 5 • Up to 2 years
|
41.7%
10/24 • Number of events 19 • Up to 2 years
|
|
Investigations
Platelet count decreased
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
8.3%
2/24 • Number of events 2 • Up to 2 years
|
|
Investigations
Weight loss
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
12.5%
3/24 • Number of events 4 • Up to 2 years
|
|
Investigations
White blood cell decreased
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 2 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
8.3%
2/24 • Number of events 3 • Up to 2 years
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
33.3%
2/6 • Number of events 2 • Up to 2 years
|
12.5%
3/24 • Number of events 3 • Up to 2 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
8.3%
2/24 • Number of events 4 • Up to 2 years
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
16.7%
4/24 • Number of events 5 • Up to 2 years
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
8.3%
2/24 • Number of events 6 • Up to 2 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
12.5%
3/24 • Number of events 7 • Up to 2 years
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
12.5%
3/24 • Number of events 4 • Up to 2 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
12.5%
3/24 • Number of events 6 • Up to 2 years
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
8.3%
2/24 • Number of events 7 • Up to 2 years
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
16.7%
4/24 • Number of events 4 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
20.0%
1/5 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 3 • Up to 2 years
|
8.3%
2/24 • Number of events 2 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
20.0%
1/5 • Number of events 1 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
16.7%
4/24 • Number of events 4 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
4.2%
1/24 • Number of events 2 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
4.2%
1/24 • Number of events 2 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Myopathy
|
20.0%
1/5 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
33.3%
2/6 • Number of events 3 • Up to 2 years
|
12.5%
3/24 • Number of events 5 • Up to 2 years
|
|
Nervous system disorders
Concentration impairment
|
20.0%
1/5 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Nervous system disorders
Dizziness
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
12.5%
3/24 • Number of events 6 • Up to 2 years
|
|
Nervous system disorders
Dysgeusia
|
20.0%
1/5 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
50.0%
3/6 • Number of events 3 • Up to 2 years
|
29.2%
7/24 • Number of events 7 • Up to 2 years
|
|
Nervous system disorders
Light headedness
|
20.0%
1/5 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Nervous system disorders
Peripheral Neuropathy
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
33.3%
2/6 • Number of events 2 • Up to 2 years
|
37.5%
9/24 • Number of events 9 • Up to 2 years
|
|
Nervous system disorders
Sciatica
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Psychiatric disorders
Insomnia
|
40.0%
2/5 • Number of events 3 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
4.2%
1/24 • Number of events 1 • Up to 2 years
|
|
Renal and urinary disorders
Hematuria
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
4.2%
1/24 • Number of events 1 • Up to 2 years
|
|
Reproductive system and breast disorders
Perineal pain
|
20.0%
1/5 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, specify
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
8.3%
2/24 • Number of events 2 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
20.8%
5/24 • Number of events 5 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
33.3%
2/6 • Number of events 2 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
20.0%
1/5 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Shortness of Breath
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
4.2%
1/24 • Number of events 1 • Up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Sore Throat
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
40.0%
2/5 • Number of events 2 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
83.3%
5/6 • Number of events 6 • Up to 2 years
|
33.3%
8/24 • Number of events 9 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
12.5%
3/24 • Number of events 3 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other,
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
8.3%
2/24 • Number of events 2 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Nail discoloration
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Nail loss
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
33.3%
2/6 • Number of events 3 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
4.2%
1/24 • Number of events 1 • Up to 2 years
|
|
Skin and subcutaneous tissue disorders
Rash
|
20.0%
1/5 • Number of events 2 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
12.5%
3/24 • Number of events 4 • Up to 2 years
|
|
Vascular disorders
Flushing
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Vascular disorders
Hematoma
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Vascular disorders
Hot flashes
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Vascular disorders
Hypotension
|
0.00%
0/5 • Up to 2 years
|
25.0%
1/4 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
12.5%
3/24 • Number of events 4 • Up to 2 years
|
|
Vascular disorders
Thromboembolic event
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
4.2%
1/24 • Number of events 1 • Up to 2 years
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Investigations
Increased Phosphorous
|
0.00%
0/5 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
16.7%
1/6 • Number of events 1 • Up to 2 years
|
0.00%
0/24 • Up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders, Other
|
20.0%
1/5 • Number of events 1 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/4 • Up to 2 years
|
0.00%
0/6 • Up to 2 years
|
16.7%
4/24 • Number of events 4 • Up to 2 years
|
Additional Information
Dr. Rahul Aggarwal, MD
University of California, San Francisco
Phone: (415) 353-9278
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place