Trial Outcomes & Findings for A Phase 2 Study With Enzastaurin Plus Chemotherapy or Placebo Plus Chemotherapy for Prostate Cancer Patients (NCT NCT00466440)
NCT ID: NCT00466440
Last Updated: 2020-11-06
Results Overview
Response using Response Evaluation Criteria In Solid Tumors (RECIST). Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD)=20% increase in sum of longest diameter of target lesions; Stable Disease (SD)=small changes that do not meet above criteria. Objective response rate (%)=number of objective responders divided by the number of participants qualified for efficacy analysis \*100, where objective responders are those participants who have met criteria either for CR or PR.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
108 participants
Primary outcome timeframe
Baseline up to 3 years
Results posted on
2020-11-06
Participant Flow
Participant milestones
| Measure |
Part 1: Docetaxel + Prednisone + Enzastaurin
Participants were treated with modified Regimen A (modified investigational): docetaxel 75 milligrams per square meter (mg/m\^2), intravenous (IV) given on Day 1 every 3 weeks, and prednisone 5 milligrams (mg) oral (po), twice daily (BID) in combination with enzastaurin, starting loading dose on Day 4.
|
Part 2: Docetaxel + Prednisone + Enzastaurin
Regimen A: docetaxel 75 mg/m\^2, IV given on Day 1 every 3 weeks and prednisone 5 mg po, BID with enzastaurin, starting loading dose 1 day prior to chemotherapy.
|
Part 2: Docetaxel + Prednisone + Placebo
Regimen B: docetaxel 75 mg/m\^2, IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po, BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po, QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
|---|---|---|---|
|
Overall Study
STARTED
|
14
|
48
|
46
|
|
Overall Study
Received at Least One Dose of Study Drug
|
14
|
47
|
41
|
|
Overall Study
COMPLETED
|
0
|
36
|
34
|
|
Overall Study
NOT COMPLETED
|
14
|
12
|
12
|
Reasons for withdrawal
| Measure |
Part 1: Docetaxel + Prednisone + Enzastaurin
Participants were treated with modified Regimen A (modified investigational): docetaxel 75 milligrams per square meter (mg/m\^2), intravenous (IV) given on Day 1 every 3 weeks, and prednisone 5 milligrams (mg) oral (po), twice daily (BID) in combination with enzastaurin, starting loading dose on Day 4.
|
Part 2: Docetaxel + Prednisone + Enzastaurin
Regimen A: docetaxel 75 mg/m\^2, IV given on Day 1 every 3 weeks and prednisone 5 mg po, BID with enzastaurin, starting loading dose 1 day prior to chemotherapy.
|
Part 2: Docetaxel + Prednisone + Placebo
Regimen B: docetaxel 75 mg/m\^2, IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po, BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po, QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
3
|
1
|
|
Overall Study
Death
|
1
|
1
|
0
|
|
Overall Study
Progressive disease
|
13
|
5
|
4
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
|
Overall Study
Physician Decision
|
0
|
1
|
2
|
|
Overall Study
Protocol entry criteria not met
|
0
|
0
|
4
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
|
Overall Study
Sponsor decision
|
0
|
0
|
1
|
Baseline Characteristics
A Phase 2 Study With Enzastaurin Plus Chemotherapy or Placebo Plus Chemotherapy for Prostate Cancer Patients
Baseline characteristics by cohort
| Measure |
Part 1: Docetaxel + Prednisone + Enzastaurin
n=14 Participants
Participants were treated with modified Regimen A (modified investigational): docetaxel 75 mg/m2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID in combination with enzastaurin, starting loading dose on Day 4.
|
Part 2: Docetaxel + Prednisone + Enzastaurin
n=48 Participants
Regimen A: docetaxel 75 mg/m\^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy.
|
Part 2: Docetaxel + Prednisone + Placebo
n=46 Participants
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
Total
n=108 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
66.8 years
STANDARD_DEVIATION 7.29 • n=5 Participants
|
69.9 years
STANDARD_DEVIATION 7.66 • n=7 Participants
|
70 years
STANDARD_DEVIATION 8.1 • n=5 Participants
|
69.54 years
STANDARD_DEVIATION 7.81 • n=4 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
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
48 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
108 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
0 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
14 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
86 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
East Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
14 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
97 Participants
n=4 Participants
|
|
Region of Enrollment
Germany
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Region of Enrollment
Italy
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline up to 3 yearsPopulation: All enrolled participants from Part 2 group, who received at least one dose of study drug. Per protocol, Part 1 was not included as it is an open-label safety lead-in portion with PK characterization.
Response using Response Evaluation Criteria In Solid Tumors (RECIST). Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD)=20% increase in sum of longest diameter of target lesions; Stable Disease (SD)=small changes that do not meet above criteria. Objective response rate (%)=number of objective responders divided by the number of participants qualified for efficacy analysis \*100, where objective responders are those participants who have met criteria either for CR or PR.
Outcome measures
| Measure |
Part 2: Docetaxel + Prednisone + Enzastaurin
n=46 Participants
Regimen A: docetaxel 75 mg/m\^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy.
|
Part 2: Docetaxel + Prednisone + Placebo
n=40 Participants
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
Part 2: Docetaxel + Prednisone + Placebo
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
|---|---|---|---|
|
Part 2: Percentage of Participants With Objective Tumor Response (Response Rate)
|
15.2 percentage of participants
Interval 7.37 to 26.69
|
15.0 percentage of participants
Interval 6.74 to 27.47
|
—
|
SECONDARY outcome
Timeframe: Baseline up to 3 monthsPopulation: The analysis population included all participants having baseline and at least 1 postbaseline PSA response within the first 3 months of treatment.
PSA is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer and in other prostate disorders. A blood test to measure PSA is considered the most effective test currently available for the early detection of prostate cancer. Decline in PSA of ≥30% from baseline within the first 3 months of treatment was calculated.
Outcome measures
| Measure |
Part 2: Docetaxel + Prednisone + Enzastaurin
n=9 Participants
Regimen A: docetaxel 75 mg/m\^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy.
|
Part 2: Docetaxel + Prednisone + Placebo
n=28 Participants
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
Part 2: Docetaxel + Prednisone + Placebo
n=29 Participants
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
|---|---|---|---|
|
Percentage of Participants Exhibiting a Decline in Prostate-Specific Androgen (PSA) From Baseline ≥30% Within First 3 Months of Treatment
|
69.2 percentage of participants
Interval 42.74 to 88.73
|
60.9 percentage of participants
Interval 47.68 to 72.97
|
72.5 percentage of participants
Interval 58.61 to 83.75
|
SECONDARY outcome
Timeframe: Baseline up to 2 monthsPopulation: Participants with a valid baseline and at least 1 postbaseline PSA measurement within the first 2 months of treatment.
PSA is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer and in other prostate disorders. A blood test to measure PSA is considered the most effective test currently available for the early detection of prostate cancer. PSA velocity is computed for each participant by means of linear regression on the logarithm of PSA. The linear regression fits a line through the logarithm of the PSA value on the y-axis, and the time from baseline on the x-axis with the baseline PSA value at time zero. The resulting slope is PSA velocity.
Outcome measures
| Measure |
Part 2: Docetaxel + Prednisone + Enzastaurin
n=13 Participants
Regimen A: docetaxel 75 mg/m\^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy.
|
Part 2: Docetaxel + Prednisone + Placebo
n=46 Participants
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
Part 2: Docetaxel + Prednisone + Placebo
n=40 Participants
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
|---|---|---|---|
|
Prostate-Specific Androgen (PSA) Velocity at 2 Months
|
-0.56 microgram per liter (ug/L) per month
Interval -0.82 to -0.29
|
-0.29 microgram per liter (ug/L) per month
Interval -0.47 to -0.1
|
-0.55 microgram per liter (ug/L) per month
Interval -0.78 to -0.32
|
SECONDARY outcome
Timeframe: Baseline up to 3 monthsPopulation: Participants with a valid baseline and at least 1 postbaseline PSA measurement within the first 3 months of treatment.
PSA is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer and in other prostate disorders. A blood test to measure PSA is considered the most effective test currently available for the early detection of prostate cancer. PSA velocity is computed for each participant by means of linear regression on the logarithm of PSA. The linear regression fits a line through the logarithm of the PSA value on the y-axis, and the time from baseline on the x-axis with the baseline PSA value at time zero. The resulting slope is PSA velocity.
Outcome measures
| Measure |
Part 2: Docetaxel + Prednisone + Enzastaurin
n=13 Participants
Regimen A: docetaxel 75 mg/m\^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy.
|
Part 2: Docetaxel + Prednisone + Placebo
n=46 Participants
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
Part 2: Docetaxel + Prednisone + Placebo
n=40 Participants
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
|---|---|---|---|
|
Prostate-Specific Androgen (PSA) Velocity at 3 Months
|
-0.45 ug/L per month
Interval -0.66 to -0.25
|
-0.30 ug/L per month
Interval -0.45 to -0.15
|
-0.45 ug/L per month
Interval -0.62 to -0.28
|
SECONDARY outcome
Timeframe: Baseline to measured PD (up to 487 days)Population: All enrolled participants from Part 2 group, who received at least one dose of study drug. Per protocol, Part 1 was not included as it is an open-label safety lead-in portion with PK characterization.
PFS was defined as the time from the date of study enrollment to the first date of objectively determined progressive disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST version 1.0). PD is ≥20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. For participants not known to have died and who did not have PD, PFS was censored at the date of the last progression-free assessment. For participants who received subsequent systemic anticancer therapy (after discontinuation from the study treatment) prior to disease progression or death, PFS was censored at the date of last progression-free assessment prior to the initiation of post-discontinuation systemic anticancer therapy. No participant completed a full cycle of therapy and thus no formal analysis was performed.
Outcome measures
| Measure |
Part 2: Docetaxel + Prednisone + Enzastaurin
n=46 Participants
Regimen A: docetaxel 75 mg/m\^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy.
|
Part 2: Docetaxel + Prednisone + Placebo
n=40 Participants
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
Part 2: Docetaxel + Prednisone + Placebo
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
|---|---|---|---|
|
Part 2: Progression Free Survival (PFS)
|
229 Days
Interval 191.0 to 263.0
|
213 Days
Interval 188.0 to 240.0
|
—
|
SECONDARY outcome
Timeframe: Baseline to death (up to 642 days)Population: All enrolled participants from Part 2 group, who received at least one dose of study drug. Per protocol, Part 1 was not included as it is an open-label safety lead-in portion with PK characterization.
Overall survival (OS) time is defined as the time from the date of diagnosis to the date of death from any cause. For participants who are still alive at the time of analysis, survival time will be censored at the last contact date.
Outcome measures
| Measure |
Part 2: Docetaxel + Prednisone + Enzastaurin
n=48 Participants
Regimen A: docetaxel 75 mg/m\^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy.
|
Part 2: Docetaxel + Prednisone + Placebo
n=46 Participants
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
Part 2: Docetaxel + Prednisone + Placebo
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
|---|---|---|---|
|
Part 2: Overall Survival (OS)
|
462 days
Interval 409.0 to 590.0
|
448 days
Interval 383.0 to 453.0
|
—
|
SECONDARY outcome
Timeframe: First objective response to PD/death/PSA returning to 50% or more than the original baseline value (up to 616 days)Population: All enrolled participants from Part 2 group, who received at least one dose of study drug. Per protocol, Part 1 was not included as it is an open-label safety lead-in portion with PK characterization.
Duration of response is defined as the time from date of objective response to progressive disease (PD) or death or prostate-specific androgen (PSA) returning to at least 50% from original baseline value.
Outcome measures
| Measure |
Part 2: Docetaxel + Prednisone + Enzastaurin
n=46 Participants
Regimen A: docetaxel 75 mg/m\^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy.
|
Part 2: Docetaxel + Prednisone + Placebo
n=40 Participants
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
Part 2: Docetaxel + Prednisone + Placebo
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
|---|---|---|---|
|
Part 2: Duration of Response
|
231 days
Interval 198.0 to 297.0
|
201 days
Interval 175.0 to 225.0
|
—
|
SECONDARY outcome
Timeframe: Baseline through 3 yearsPopulation: The analysis population was defined as all enrolled participants who received at least one dose of study drug.
A listing of serious AEs (SAEs) and all other non-serious AEs is included in the Reported Adverse Event Module.
Outcome measures
| Measure |
Part 2: Docetaxel + Prednisone + Enzastaurin
n=14 Participants
Regimen A: docetaxel 75 mg/m\^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy.
|
Part 2: Docetaxel + Prednisone + Placebo
n=47 Participants
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
Part 2: Docetaxel + Prednisone + Placebo
n=41 Participants
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
|---|---|---|---|
|
Number of Participants With Adverse Events (AEs)
SAEs
|
8 Participants
|
16 Participants
|
14 Participants
|
|
Number of Participants With Adverse Events (AEs)
Other Non-Serious AEs
|
14 Participants
|
47 Participants
|
41 Participants
|
SECONDARY outcome
Timeframe: Part 1: Cycle 1, Day 21 - predose 2, 4, 6, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 2, 3, 4, 8, and 24 hours postdosePopulation: For Part 1, pharmacokinetic analyses were conducted for individual participants who received at least one dose of study drug and had pharmacokinetic samples collected.
Cmax,ss was calculated using concentration versus time data of enzastaurin, LSN326020, and total analyte (enzastaurin + LSN326020). Data are reported as Geometric Mean and Geometric Coefficient of Variation (%).
Outcome measures
| Measure |
Part 2: Docetaxel + Prednisone + Enzastaurin
n=9 Participants
Regimen A: docetaxel 75 mg/m\^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy.
|
Part 2: Docetaxel + Prednisone + Placebo
n=7 Participants
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
Part 2: Docetaxel + Prednisone + Placebo
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
|---|---|---|---|
|
Part I: Pharmacokinetic (PK) Parameter: Maximum Observed Drug Concentration During a Dosing Interval at Steady State (Cmax,ss) of Enzastaurin, LSN326020, and Total Analyte (Enzastaurin + LSN326020)
Enzastaurin
|
870 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 84
|
778 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 39
|
—
|
|
Part I: Pharmacokinetic (PK) Parameter: Maximum Observed Drug Concentration During a Dosing Interval at Steady State (Cmax,ss) of Enzastaurin, LSN326020, and Total Analyte (Enzastaurin + LSN326020)
LSN326020
|
664 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 45
|
667 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 30
|
—
|
|
Part I: Pharmacokinetic (PK) Parameter: Maximum Observed Drug Concentration During a Dosing Interval at Steady State (Cmax,ss) of Enzastaurin, LSN326020, and Total Analyte (Enzastaurin + LSN326020)
Total Analyte
|
1540 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 62
|
1450 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 32
|
—
|
SECONDARY outcome
Timeframe: Part 1: Cycle 1, Day 21 - predose 2, 4, 6, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 2, 3, 4, 8, and 24 hours postdose; Part 2: Cycle 2, Day 1 - predose, 1-3, and 4-9 hours postdosePopulation: Pharmacokinetic analyses were conducted for individual participants who received at least one dose of study drug and had pharmacokinetic samples collected.
AUCτ,ss was calculated using concentration versus time data of enzastaurin, LSN326020, and total analyte (enzastaurin + LSN326020). Data are reported as Geometric Mean and Geometric Coefficient of Variation (%).
Outcome measures
| Measure |
Part 2: Docetaxel + Prednisone + Enzastaurin
n=7 Participants
Regimen A: docetaxel 75 mg/m\^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy.
|
Part 2: Docetaxel + Prednisone + Placebo
n=6 Participants
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
Part 2: Docetaxel + Prednisone + Placebo
n=9 Participants
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
|---|---|---|---|
|
Pharmacokinetic (PK) Parameter: Area Under the Concentration Versus Time Curve During 1 Dosing Interval at Steady State (AUCτ,ss) of Enzastaurin, LSN326020, and Total Analyte (Enzastaurin + LSN326020)
Enzastaurin
|
12900 nanomole*hour per liter (nmol*hr/L)
Geometric Coefficient of Variation 79
|
13100 nanomole*hour per liter (nmol*hr/L)
Geometric Coefficient of Variation 26
|
20800 nanomole*hour per liter (nmol*hr/L)
Geometric Coefficient of Variation 104
|
|
Pharmacokinetic (PK) Parameter: Area Under the Concentration Versus Time Curve During 1 Dosing Interval at Steady State (AUCτ,ss) of Enzastaurin, LSN326020, and Total Analyte (Enzastaurin + LSN326020)
LSN326020
|
15200 nanomole*hour per liter (nmol*hr/L)
Geometric Coefficient of Variation 35
|
15700 nanomole*hour per liter (nmol*hr/L)
Geometric Coefficient of Variation 20
|
24800 nanomole*hour per liter (nmol*hr/L)
Geometric Coefficient of Variation 52
|
|
Pharmacokinetic (PK) Parameter: Area Under the Concentration Versus Time Curve During 1 Dosing Interval at Steady State (AUCτ,ss) of Enzastaurin, LSN326020, and Total Analyte (Enzastaurin + LSN326020)
Total Analyte
|
28700 nanomole*hour per liter (nmol*hr/L)
Geometric Coefficient of Variation 49
|
29000 nanomole*hour per liter (nmol*hr/L)
Geometric Coefficient of Variation 18
|
47800 nanomole*hour per liter (nmol*hr/L)
Geometric Coefficient of Variation 74
|
SECONDARY outcome
Timeframe: Part 1: Cycle 1, Day 1 - predose 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdosePopulation: For Part 1, pharmacokinetic analyses were conducted for individual participants who received at least one dose of study drug and had pharmacokinetic samples collected.
Cmax was calculated using concentration versus time data of docetaxel. Data are reported as Geometric Mean and Geometric Coefficient of Variation (%).
Outcome measures
| Measure |
Part 2: Docetaxel + Prednisone + Enzastaurin
n=13 Participants
Regimen A: docetaxel 75 mg/m\^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy.
|
Part 2: Docetaxel + Prednisone + Placebo
n=10 Participants
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
Part 2: Docetaxel + Prednisone + Placebo
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
|---|---|---|---|
|
Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Docetaxel
|
2230 nanograms per millimeter (ng/mL)
Geometric Coefficient of Variation 21
|
1840 nanograms per millimeter (ng/mL)
Geometric Coefficient of Variation 22
|
—
|
SECONDARY outcome
Timeframe: Part 1: Cycle 1, Day 1 - predose 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdosePopulation: For Part 1, pharmacokinetic analyses were conducted for individual participants who received at least one dose of study drug and had pharmacokinetic samples collected.
AUC(0-∞) was calculated using concentration versus time data of docetaxel. Data are reported as Geometric Mean and Geometric Coefficient of Variation (%).
Outcome measures
| Measure |
Part 2: Docetaxel + Prednisone + Enzastaurin
n=13 Participants
Regimen A: docetaxel 75 mg/m\^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy.
|
Part 2: Docetaxel + Prednisone + Placebo
n=10 Participants
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
Part 2: Docetaxel + Prednisone + Placebo
Regimen B: docetaxel 75 mg/m\^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
|---|---|---|---|
|
Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-∞]) of Docetaxel
|
2350 ng*h/mL
Geometric Coefficient of Variation 26
|
1750 ng*h/mL
Geometric Coefficient of Variation 20
|
—
|
SECONDARY outcome
Timeframe: Baseline up to 36 monthsPopulation: Data were not collected for any participant due to low samples.
Pharmacogenomic (PGx) work on S032 was cancelled due to the limited number of tissue samples collected and the lack of clinical efficacy (responders) to enzastaurin. Potential biomarkers would have been assessed by dividing participants into low and high expression classes.
Outcome measures
Outcome data not reported
Adverse Events
Part 1: Docetaxel + Prednisone + Enzastaurin
Serious events: 8 serious events
Other events: 14 other events
Deaths: 0 deaths
Part 2: Docetaxel + Prednisone + Enzastaurin
Serious events: 16 serious events
Other events: 47 other events
Deaths: 0 deaths
Part 2: Docetaxel + Prednisone + Placebo
Serious events: 14 serious events
Other events: 41 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Part 1: Docetaxel + Prednisone + Enzastaurin
n=14 participants at risk
Participants were treated with modified Regimen A (modified investigational): docetaxel 75 milligrams per square meter (mg/m\^2), intravenous (IV) given on Day 1 every 3 weeks, and prednisone 5 milligrams (mg) oral (po), twice daily (BID) in combination with enzastaurin, starting loading dose on Day 4.
|
Part 2: Docetaxel + Prednisone + Enzastaurin
n=47 participants at risk
Regimen A: docetaxel 75 mg/m\^2, IV given on Day 1 every 3 weeks and prednisone 5 mg po, BID with enzastaurin, starting loading dose 1 day prior to chemotherapy.
|
Part 2: Docetaxel + Prednisone + Placebo
n=41 participants at risk
Regimen B: docetaxel 75 mg/m\^2, IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po, BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po, QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
14.3%
2/14 • Number of events 3
|
12.8%
6/47 • Number of events 7
|
4.9%
2/41 • Number of events 2
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/14
|
4.3%
2/47 • Number of events 2
|
0.00%
0/41
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Gastrointestinal disorders
Anal fistula
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/14
|
0.00%
0/47
|
4.9%
2/41 • Number of events 2
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/14
|
6.4%
3/47 • Number of events 3
|
2.4%
1/41 • Number of events 1
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Gastrointestinal disorders
Faecaloma
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
4.9%
2/41 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
2.4%
1/41 • Number of events 1
|
|
General disorders
Asthenia
|
0.00%
0/14
|
4.3%
2/47 • Number of events 2
|
2.4%
1/41 • Number of events 1
|
|
General disorders
Chest pain
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
2.4%
1/41 • Number of events 1
|
|
General disorders
Extravasation
|
14.3%
2/14 • Number of events 2
|
0.00%
0/47
|
0.00%
0/41
|
|
General disorders
Pain
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
General disorders
Pyrexia
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Infections and infestations
Fungaemia
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Infections and infestations
Infection
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Infections and infestations
Pelvic abscess
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Infections and infestations
Pneumonia
|
0.00%
0/14
|
6.4%
3/47 • Number of events 3
|
4.9%
2/41 • Number of events 2
|
|
Infections and infestations
Sepsis
|
7.1%
1/14 • Number of events 1
|
4.3%
2/47 • Number of events 2
|
0.00%
0/41
|
|
Infections and infestations
Septic shock
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
2.4%
1/41 • Number of events 1
|
|
Injury, poisoning and procedural complications
Wound
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Metabolism and nutrition disorders
Cachexia
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/14
|
4.3%
2/47 • Number of events 2
|
2.4%
1/41 • Number of events 1
|
|
Metabolism and nutrition disorders
Fluid overload
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/14
|
4.3%
2/47 • Number of events 2
|
0.00%
0/41
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/14
|
2.1%
1/47 • Number of events 2
|
0.00%
0/41
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal carcinoma
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Nervous system disorders
Dizziness
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Nervous system disorders
Hydrocephalus
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Nervous system disorders
Myasthenia gravis
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Nervous system disorders
Syncope
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Renal and urinary disorders
Cystitis haemorrhagic
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
2.4%
1/41 • Number of events 1
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Renal and urinary disorders
Renal failure
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Renal and urinary disorders
Ureteric obstruction
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
2.4%
1/41 • Number of events 1
|
|
Renal and urinary disorders
Urinary tract obstruction
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/14
|
0.00%
0/47
|
4.9%
2/41 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
2.4%
1/41 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary fibrosis
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
0.00%
0/14
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/14
|
4.3%
2/47 • Number of events 2
|
2.4%
1/41 • Number of events 1
|
|
Vascular disorders
Thrombosis
|
14.3%
2/14 • Number of events 2
|
0.00%
0/47
|
0.00%
0/41
|
Other adverse events
| Measure |
Part 1: Docetaxel + Prednisone + Enzastaurin
n=14 participants at risk
Participants were treated with modified Regimen A (modified investigational): docetaxel 75 milligrams per square meter (mg/m\^2), intravenous (IV) given on Day 1 every 3 weeks, and prednisone 5 milligrams (mg) oral (po), twice daily (BID) in combination with enzastaurin, starting loading dose on Day 4.
|
Part 2: Docetaxel + Prednisone + Enzastaurin
n=47 participants at risk
Regimen A: docetaxel 75 mg/m\^2, IV given on Day 1 every 3 weeks and prednisone 5 mg po, BID with enzastaurin, starting loading dose 1 day prior to chemotherapy.
|
Part 2: Docetaxel + Prednisone + Placebo
n=41 participants at risk
Regimen B: docetaxel 75 mg/m\^2, IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po, BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po, QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
7.1%
1/14 • Number of events 1
|
29.8%
14/47 • Number of events 17
|
17.1%
7/41 • Number of events 7
|
|
Blood and lymphatic system disorders
Leukopenia
|
14.3%
2/14 • Number of events 3
|
19.1%
9/47 • Number of events 35
|
12.2%
5/41 • Number of events 10
|
|
Blood and lymphatic system disorders
Lymphopenia
|
64.3%
9/14 • Number of events 11
|
10.6%
5/47 • Number of events 7
|
26.8%
11/41 • Number of events 14
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/14
|
38.3%
18/47 • Number of events 55
|
34.1%
14/41 • Number of events 19
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
7.1%
1/14 • Number of events 2
|
8.5%
4/47 • Number of events 4
|
4.9%
2/41 • Number of events 4
|
|
Cardiac disorders
Cardio-Respiratory arrest
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Cardiac disorders
Supraventricular tachycardia
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Eye disorders
Diplopia
|
7.1%
1/14 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
2.4%
1/41 • Number of events 1
|
|
Eye disorders
Dry eye
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Eye disorders
Lacrimation increased
|
14.3%
2/14 • Number of events 2
|
6.4%
3/47 • Number of events 3
|
2.4%
1/41 • Number of events 1
|
|
Eye disorders
Strabismus
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Eye disorders
Vision blurred
|
21.4%
3/14 • Number of events 3
|
2.1%
1/47 • Number of events 1
|
9.8%
4/41 • Number of events 4
|
|
Gastrointestinal disorders
Abdominal discomfort
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Gastrointestinal disorders
Abdominal distension
|
14.3%
2/14 • Number of events 2
|
2.1%
1/47 • Number of events 2
|
2.4%
1/41 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
14.3%
2/14 • Number of events 5
|
17.0%
8/47 • Number of events 10
|
7.3%
3/41 • Number of events 3
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/14
|
6.4%
3/47 • Number of events 3
|
0.00%
0/41
|
|
Gastrointestinal disorders
Ascites
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Gastrointestinal disorders
Constipation
|
35.7%
5/14 • Number of events 6
|
23.4%
11/47 • Number of events 16
|
14.6%
6/41 • Number of events 7
|
|
Gastrointestinal disorders
Diarrhoea
|
50.0%
7/14 • Number of events 7
|
46.8%
22/47 • Number of events 35
|
36.6%
15/41 • Number of events 20
|
|
Gastrointestinal disorders
Dry mouth
|
7.1%
1/14 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
2.4%
1/41 • Number of events 1
|
|
Gastrointestinal disorders
Dyspepsia
|
21.4%
3/14 • Number of events 3
|
8.5%
4/47 • Number of events 5
|
9.8%
4/41 • Number of events 5
|
|
Gastrointestinal disorders
Faecal incontinence
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
7.1%
1/14 • Number of events 1
|
4.3%
2/47 • Number of events 2
|
0.00%
0/41
|
|
Gastrointestinal disorders
Haemorrhoids
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Gastrointestinal disorders
Lip dry
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Gastrointestinal disorders
Nausea
|
50.0%
7/14 • Number of events 8
|
44.7%
21/47 • Number of events 33
|
26.8%
11/41 • Number of events 14
|
|
Gastrointestinal disorders
Oral disorder
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
7.1%
1/14 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
2.4%
1/41 • Number of events 1
|
|
Gastrointestinal disorders
Sensitivity of teeth
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/14
|
10.6%
5/47 • Number of events 5
|
4.9%
2/41 • Number of events 3
|
|
Gastrointestinal disorders
Vomiting
|
7.1%
1/14 • Number of events 1
|
29.8%
14/47 • Number of events 16
|
9.8%
4/41 • Number of events 4
|
|
General disorders
Asthenia
|
0.00%
0/14
|
21.3%
10/47 • Number of events 13
|
7.3%
3/41 • Number of events 3
|
|
General disorders
Extravasation
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
General disorders
Fatigue
|
50.0%
7/14 • Number of events 9
|
55.3%
26/47 • Number of events 34
|
61.0%
25/41 • Number of events 32
|
|
General disorders
Feeling cold
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
4.9%
2/41 • Number of events 2
|
|
General disorders
Gait disturbance
|
7.1%
1/14 • Number of events 1
|
4.3%
2/47 • Number of events 2
|
7.3%
3/41 • Number of events 3
|
|
General disorders
Malaise
|
0.00%
0/14
|
10.6%
5/47 • Number of events 6
|
4.9%
2/41 • Number of events 2
|
|
General disorders
Mucosal inflammation
|
7.1%
1/14 • Number of events 1
|
4.3%
2/47 • Number of events 2
|
4.9%
2/41 • Number of events 2
|
|
General disorders
Oedema
|
14.3%
2/14 • Number of events 2
|
2.1%
1/47 • Number of events 1
|
4.9%
2/41 • Number of events 2
|
|
General disorders
Oedema peripheral
|
0.00%
0/14
|
17.0%
8/47 • Number of events 10
|
22.0%
9/41 • Number of events 10
|
|
General disorders
Pain
|
7.1%
1/14 • Number of events 1
|
4.3%
2/47 • Number of events 2
|
2.4%
1/41 • Number of events 2
|
|
Infections and infestations
Cellulitis
|
7.1%
1/14 • Number of events 1
|
2.1%
1/47 • Number of events 2
|
0.00%
0/41
|
|
Infections and infestations
Intervertebral discitis
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Infections and infestations
Opportunistic infection
|
14.3%
2/14 • Number of events 2
|
0.00%
0/47
|
0.00%
0/41
|
|
Infections and infestations
Oral herpes
|
14.3%
2/14 • Number of events 2
|
0.00%
0/47
|
0.00%
0/41
|
|
Infections and infestations
Rhinitis
|
0.00%
0/14
|
6.4%
3/47 • Number of events 3
|
2.4%
1/41 • Number of events 1
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/14
|
8.5%
4/47 • Number of events 4
|
4.9%
2/41 • Number of events 2
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/14
|
6.4%
3/47 • Number of events 3
|
0.00%
0/41
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/14
|
12.8%
6/47 • Number of events 7
|
4.9%
2/41 • Number of events 2
|
|
Injury, poisoning and procedural complications
Injury
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/14
|
14.9%
7/47 • Number of events 10
|
2.4%
1/41 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
14.3%
2/14 • Number of events 3
|
19.1%
9/47 • Number of events 13
|
17.1%
7/41 • Number of events 8
|
|
Investigations
Blood albumin decreased
|
7.1%
1/14 • Number of events 1
|
4.3%
2/47 • Number of events 2
|
0.00%
0/41
|
|
Investigations
Blood alkaline phosphatase increased
|
14.3%
2/14 • Number of events 2
|
6.4%
3/47 • Number of events 3
|
0.00%
0/41
|
|
Investigations
Blood calcium decreased
|
21.4%
3/14 • Number of events 3
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Investigations
Blood creatinine increased
|
42.9%
6/14 • Number of events 7
|
12.8%
6/47 • Number of events 7
|
4.9%
2/41 • Number of events 2
|
|
Investigations
Blood glucose increased
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Investigations
Blood phosphorus decreased
|
14.3%
2/14 • Number of events 2
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Investigations
Blood potassium decreased
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Investigations
Blood potassium increased
|
21.4%
3/14 • Number of events 4
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Investigations
Blood sodium decreased
|
7.1%
1/14 • Number of events 2
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Investigations
Blood uric acid decreased
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Investigations
Blood uric acid increased
|
7.1%
1/14 • Number of events 1
|
2.1%
1/47 • Number of events 2
|
2.4%
1/41 • Number of events 1
|
|
Investigations
Haemoglobin decreased
|
35.7%
5/14 • Number of events 5
|
10.6%
5/47 • Number of events 5
|
22.0%
9/41 • Number of events 11
|
|
Investigations
Neutrophil count decreased
|
21.4%
3/14 • Number of events 3
|
4.3%
2/47 • Number of events 6
|
9.8%
4/41 • Number of events 4
|
|
Investigations
Platelet count decreased
|
7.1%
1/14 • Number of events 1
|
2.1%
1/47 • Number of events 2
|
2.4%
1/41 • Number of events 1
|
|
Investigations
Weight decreased
|
14.3%
2/14 • Number of events 2
|
8.5%
4/47 • Number of events 4
|
17.1%
7/41 • Number of events 7
|
|
Investigations
Weight increased
|
0.00%
0/14
|
2.1%
1/47 • Number of events 1
|
7.3%
3/41 • Number of events 3
|
|
Investigations
White blood cell count decreased
|
21.4%
3/14 • Number of events 4
|
8.5%
4/47 • Number of events 8
|
4.9%
2/41 • Number of events 3
|
|
Metabolism and nutrition disorders
Anorexia
|
28.6%
4/14 • Number of events 4
|
25.5%
12/47 • Number of events 16
|
36.6%
15/41 • Number of events 16
|
|
Metabolism and nutrition disorders
Decreased appetite
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/14
|
14.9%
7/47 • Number of events 9
|
7.3%
3/41 • Number of events 4
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
7.1%
1/14 • Number of events 1
|
29.8%
14/47 • Number of events 17
|
19.5%
8/41 • Number of events 13
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
14.3%
2/14 • Number of events 2
|
8.5%
4/47 • Number of events 6
|
2.4%
1/41 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
14.3%
2/14 • Number of events 2
|
4.3%
2/47 • Number of events 2
|
4.9%
2/41 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
7.1%
1/14 • Number of events 1
|
12.8%
6/47 • Number of events 8
|
9.8%
4/41 • Number of events 5
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/14
|
6.4%
3/47 • Number of events 4
|
7.3%
3/41 • Number of events 4
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/14
|
4.3%
2/47 • Number of events 2
|
9.8%
4/41 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
28.6%
4/14 • Number of events 5
|
12.8%
6/47 • Number of events 7
|
19.5%
8/41 • Number of events 8
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
14.3%
2/14 • Number of events 2
|
17.0%
8/47 • Number of events 9
|
19.5%
8/41 • Number of events 8
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/14
|
4.3%
2/47 • Number of events 2
|
7.3%
3/41 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Joint stiffness
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
7.1%
1/14 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
4.9%
2/41 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
14.3%
2/14 • Number of events 2
|
12.8%
6/47 • Number of events 7
|
2.4%
1/41 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
14.3%
2/14 • Number of events 2
|
10.6%
5/47 • Number of events 5
|
4.9%
2/41 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/14
|
6.4%
3/47 • Number of events 5
|
7.3%
3/41 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
21.4%
3/14 • Number of events 3
|
12.8%
6/47 • Number of events 8
|
17.1%
7/41 • Number of events 7
|
|
Musculoskeletal and connective tissue disorders
Trigger finger
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Nervous system disorders
Dizziness
|
14.3%
2/14 • Number of events 2
|
23.4%
11/47 • Number of events 16
|
22.0%
9/41 • Number of events 11
|
|
Nervous system disorders
Dysgeusia
|
21.4%
3/14 • Number of events 3
|
29.8%
14/47 • Number of events 18
|
19.5%
8/41 • Number of events 8
|
|
Nervous system disorders
Headache
|
21.4%
3/14 • Number of events 3
|
6.4%
3/47 • Number of events 3
|
2.4%
1/41 • Number of events 1
|
|
Nervous system disorders
Neuropathy peripheral
|
28.6%
4/14 • Number of events 4
|
12.8%
6/47 • Number of events 8
|
19.5%
8/41 • Number of events 11
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/14
|
6.4%
3/47 • Number of events 3
|
7.3%
3/41 • Number of events 3
|
|
Nervous system disorders
Sciatica
|
14.3%
2/14 • Number of events 2
|
0.00%
0/47
|
0.00%
0/41
|
|
Nervous system disorders
Spinal cord compression
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/14
|
6.4%
3/47 • Number of events 3
|
2.4%
1/41 • Number of events 1
|
|
Psychiatric disorders
Depression
|
7.1%
1/14 • Number of events 1
|
6.4%
3/47 • Number of events 3
|
2.4%
1/41 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
14.3%
2/14 • Number of events 2
|
6.4%
3/47 • Number of events 3
|
7.3%
3/41 • Number of events 3
|
|
Renal and urinary disorders
Haematuria
|
7.1%
1/14 • Number of events 2
|
8.5%
4/47 • Number of events 4
|
4.9%
2/41 • Number of events 2
|
|
Renal and urinary disorders
Nocturia
|
14.3%
2/14 • Number of events 2
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Renal and urinary disorders
Pollakiuria
|
7.1%
1/14 • Number of events 1
|
4.3%
2/47 • Number of events 2
|
9.8%
4/41 • Number of events 5
|
|
Renal and urinary disorders
Urinary bladder haemorrhage
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/14
|
0.00%
0/47
|
7.3%
3/41 • Number of events 3
|
|
Reproductive system and breast disorders
Pelvic pain
|
7.1%
1/14 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
2.4%
1/41 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
21.4%
3/14 • Number of events 3
|
8.5%
4/47 • Number of events 6
|
24.4%
10/41 • Number of events 11
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
14.3%
2/14 • Number of events 2
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
35.7%
5/14 • Number of events 6
|
19.1%
9/47 • Number of events 10
|
14.6%
6/41 • Number of events 7
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
21.4%
3/14 • Number of events 3
|
2.1%
1/47 • Number of events 1
|
0.00%
0/41
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/14
|
6.4%
3/47 • Number of events 4
|
0.00%
0/41
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/14
|
6.4%
3/47 • Number of events 3
|
2.4%
1/41 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
0.00%
0/14
|
6.4%
3/47 • Number of events 3
|
9.8%
4/41 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
7.1%
1/14 • Number of events 1
|
4.3%
2/47 • Number of events 2
|
2.4%
1/41 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
0.00%
0/14
|
6.4%
3/47 • Number of events 3
|
0.00%
0/41
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
85.7%
12/14 • Number of events 12
|
44.7%
21/47 • Number of events 21
|
53.7%
22/41 • Number of events 23
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
14.3%
2/14 • Number of events 2
|
4.3%
2/47 • Number of events 2
|
4.9%
2/41 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/14
|
8.5%
4/47 • Number of events 4
|
2.4%
1/41 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Nail discolouration
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
2.4%
1/41 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
35.7%
5/14 • Number of events 5
|
23.4%
11/47 • Number of events 11
|
24.4%
10/41 • Number of events 10
|
|
Skin and subcutaneous tissue disorders
Palmar-Plantar erythrodysaesthesia syndrome
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/14
|
10.6%
5/47 • Number of events 5
|
12.2%
5/41 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
0.00%
0/14
|
6.4%
3/47 • Number of events 3
|
0.00%
0/41
|
|
Skin and subcutaneous tissue disorders
Swelling face
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Surgical and medical procedures
Surgery
|
7.1%
1/14 • Number of events 1
|
0.00%
0/47
|
0.00%
0/41
|
|
Vascular disorders
Flushing
|
7.1%
1/14 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
4.9%
2/41 • Number of events 2
|
|
Vascular disorders
Hypotension
|
7.1%
1/14 • Number of events 1
|
12.8%
6/47 • Number of events 8
|
7.3%
3/41 • Number of events 3
|
|
Vascular disorders
Phlebitis
|
0.00%
0/14
|
0.00%
0/47
|
7.3%
3/41 • Number of events 4
|
|
Vascular disorders
Thrombosis
|
7.1%
1/14 • Number of events 1
|
4.3%
2/47 • Number of events 2
|
0.00%
0/41
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60