Phase 2 Trial of Enzastaurin in Prostate Cancer in Participants Who Have Had Hormonal and Chemotherapy

Objective responders were defined as participants (pts) in Cohort 1 who met prostate-specific antigen (PSA) response criteria. PSA Complete response (CR) was defined as a decrease in PSA to an undetectable level (\<0.2 ng/mL) confirmed by a second value obtained at least 4 weeks apart and without clinical or radiographic evidence of disease. PSA Partial Response (PR) was defined as a decrease in PSA of \>=50% at any time during the study. The decline of \>=50% in PSA must be from a baseline value of \>5 ng/mL and must be confirmed by a second value obtained at least 4 weeks apart and without clinical or radiographic evidence of disease.

Time frame: Baseline to Measured Progressive Disease, Death, Unacceptable Toxicities, or Study Closure Whichever Occurred First (up to 56 weeks)

Population: Participants in Cohort 1 with a valid baseline and at least one post-baseline PSA assessment.

PFS was defined as the time from date of enrollment to first occurrence of (1) tumor progression (defined per Response Evaluation Criteria In Solid Tumors \[RECIST\]) for soft tissue lesions, and/or appearance of \>=2 new lesions on bone scan (confirmed \>=6 weeks later); (2) skeletal event (pathological bone fracture and/or need for palliative radiotherapy); (3) symptomatic progression (worsening of Eastern Cooperative Oncology Group (ECOG) performance status (PS) and/or weight loss \>10% from baseline and/or increase in analgesic consumption and pain); or (4) Death due to any cause. PFS was censored at date of last objective progression-free observation for participants who were still alive and had not progressed. Participants who took any subsequent systemic anticancer therapy prior to progression or death were censored at date of last objective progression-free disease assessment prior to the date of the subsequent systemic anticancer therapy.

Time frame: baseline to first occurrence of tumor progression, skeletal event, symptomatic progression, or death (up to 31.3 weeks)

Population: Participants in Cohort 2 who received at least 1 dose of enzastaurin. Two participants were censored.

Duration of response was the date of first objective assessment of CR or PR to the date of first progression or death due to any cause. Progression of disease defined as:1) PSA progression: (a) in whom a 50% decline in PSA has not been achieved, defined as 25% increase over baseline or nadir whichever is lower and an increase in the absolute value of PSA level by 5 ng/mL and confirmed by another PSA at least 4 weeks apart, (b) in whom a 50% decline in PSA has been achieved, defined as 50% increase over the nadir and an increase in the absolute value of PSA level by 5 ng/mL and confirmed by another PSA level at least 4 weeks apart. 2) Objective Progression defined as radiographic evidence of metastatic disease irrespective of PSA value or 3) death due to any cause. Duration of response was censored on the date of discontinuation or last assessment for those participants who were alive without progression.

Time frame: time of response to progressive disease, death, unacceptable toxicities, or study closure whichever occurred first (up to 56 weeks)

Population: Participants in Cohort 1 with a CR or PR who had a valid baseline and at least one post-baseline PSA assessment.

Number of participants exhibiting a PSA level decline from baseline of greater than or equal to 30% within the first 3 months of study.

Time frame: baseline to 3 months

Population: Participants Cohort 1 with a valid baseline and at least one post-baseline PSA assessment.

Progression free survival (PFS) is defined as the time from the date of enrollment to the first occurrence of PSA progression or objective progression defined as development of radiographic evidence of metastatic disease irrespective of PSA value or death due to any cause. PSA progression is defined as (a) for participants in whom a 50% decline in PSA has not been achieved, this is defined as 25% increase over baseline or nadir whichever is lower and an increase in the absolute value of PSA level by 5 ng/mL that is confirmed by another value of PSA confirmed at least 4 weeks apart; (b) for participants in whom a 50% decline in PSA has been achieved, this is defined as 50% increase over the nadir and an increase in the absolute value of PSA level by 5 ng/mL that is confirmed by another PSA level at least 4 weeks apart.

Time frame: baseline to date of disease progression, death, unacceptable toxicities, or study closure whichever occurred first (up to 56 weeks)

Population: Participants in Cohort 1 with a valid baseline and at least one post-baseline PSA assessment. Two participants were censored.

PSA velocity is defined as the rate of change in the PSA level during the first 2 and 3 months of the study.

Time frame: baseline, 2 months and 3 months

Population: Participants in Cohort 1 with a valid baseline and at least one post-baseline PSA measurement within the first 2 and 3 months of treatment, respectively.

Number of participants exhibiting a PSA level decline from baseline of greater than or equal to 30% within the first 3 months of study.

Time frame: baseline to 3 months

Population: Participants in Cohort 2 with a valid baseline and at least one post-baseline PSA measurement within the first 3 months of treatment.

Duration of response was the date of first objective assessment of CR or PR to the date of first progression or death due to any cause. Progression of disease defined as:1) PSA progression: (a) in whom a 50% decline in PSA has not been achieved, defined as 25% increase over baseline or nadir whichever is lower and an increase in the absolute value of PSA level by 5 ng/mL and confirmed by another PSA at least 4 weeks apart, (b) in whom a 50% decline in PSA has been achieved, defined as 50% increase over the nadir and an increase in the absolute value of PSA level by 5 ng/mL and confirmed by another PSA level at least 4 weeks apart. 2) Objective Progression defined as radiographic evidence of metastatic disease irrespective of PSA value. 3) death due to any cause. Duration of response was censored on the date of discontinuation or last assessment for those participants who were alive without progression.

Time frame: time of response to first occurrence of tumor progression, skeletal event, symptomatic progression, or death (up to 31.3 months)

Population: Zero participants were analyzed. Duration of response was not evaluable, as there were no participants with CR or PR in Cohort 2.

Objective responders in Cohort 2 met either CR or PR for composite criteria of PSA and RECIST. CR was defined as a decrease in PSA to an undetectable level (\<0.2 ng/mL) confirmed by a second value at least 4 weeks apart and without clinical or radiographic evidence of disease per RECIST and normalization of bone scan. Bone only disease CR is normalization of bone scan with achievement of a nondetectable PSA confirmed 4-weeks after initial undetectable PSA. PR was defined as a decrease from baseline by 50% in PSA at any time during the study and confirmed by a second value at least 4 weeks apart and having at least a 30% decrease in sum of longest diameter of target lesions per RECIST and stable or improved bone scan.

Time frame: baseline to first occurrence of tumor progression, skeletal event, symptomatic progression, or death (up to 31.3 months)

Population: Participants in Cohort 2 with a valid baseline and at least one post-baseline PSA assessment.

Overall survival is the duration from enrollment to death. For participants who were alive, overall survival was censored at the last contact.

Time frame: baseline to date of death from any cause (up to 69.6 weeks)

Population: Participants in Cohort 2 who received at least 1 dose of enzastaurin. Number of censored participants is 36.

Percentage of participants who did not meet the following criteria at 6 months and at 12 months: disease progression defined per RECIST for soft tissue lesions and/or the appearance of 2 or more new lesions on bone scan, or skeletal event (any pathological bone fracture, and/or need for palliative radiotherapy), or symptomatic progression (worsening ECOG performance status) and/or weight loss \>10% from baseline and/or increase in analgesic consumption and pain, or death due to any cause. PFS was censored at the date of the most recent assessment for those who were still alive at the time of analysis and did not have evidence of tumor progression. Participants who took any subsequent systemic anticancer therapy prior to progression or death, PFS was censored at the date of the last objective progression-free disease assessment prior to the date of the subsequent systemic anticancer therapy. Percent=(number of participants meeting PFS criteria/number of randomized)x100.

Time frame: 6 months and 12 months

Population: Participants in Cohort 2 who received at least 1 dose of enzastaurin. Two participants were censored.

PSA velocity is defined as the rate of change in the PSA level during the first 2 and 3 months of the study.

Time frame: baseline, 2 months and 3 months

Population: Participants in Cohort 2 with a valid baseline and at least one post-baseline PSA measurement within the first 2 and 3 months of treatment, respectively.