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

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00428714
• Collaborator: (none)
• Enrollment: 73
• Locations: 11
• Arms: 2
• Duration (Months): 48
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose is to see how quickly two different types of prostate cancer participants respond when taking enzastaurin.

Cohort 1 - asymptomatic participants with androgen-independent prostate-specific antigen (PSA)-progressive disease without clinical or radiographic evidence of metastatic disease.

Cohort 2 - participants with androgen-independent metastatic prostate cancer (documented bone or soft tissue metastases) with rising PSA, clinical, radiographic disease progression following one prior docetaxel-based regimen

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: enzastaurin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 73 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Trial Oral Enzastaurin in Prostate Cancer Patients Who Have Rising PSA (1) During Hormonal Manipulation and (2) After First-Line Cytotoxic Chemotherapy
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Enzastaurin-Cohort 1 Chemo-naive participants who had androgen-independent prostate cancer with rising prostate-specific antigen (PSA) levels but no clinical or radiographic evidence of metastatic disease. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.	Drug: enzastaurin; Administered orally; Other Names: LY317615
Experimental: Enzastaurin-Cohort 2 Participants with progressed, metastatic prostate cancer who had received prior treatment with a docetaxel-containing agent. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.	Drug: enzastaurin; Administered orally; Other Names: LY317615

Outcome Measures

Primary Outcome Measures

1. Cohort 1 - Number of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate) [Baseline to Measured Progressive Disease, Death, Unacceptable Toxicities, or Study Closure Whichever Occurred First (up to 56 weeks)]

   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.

2. Cohort 2 - Progression-free Survival (PFS)-Overall [baseline to first occurrence of tumor progression, skeletal event, symptomatic progression, or death (up to 31.3 weeks)]

   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.

Secondary Outcome Measures

1. Cohort 1 - Number of Participants With a 3-month PSA Level Decline of Greater Than or Equal to 30% [baseline to 3 months]

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

2. Cohort 1 - PSA Velocity [baseline, 2 months and 3 months]

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

3. Cohort 1 - Progression-free Survival (PFS)-Overall [baseline to date of disease progression, death, unacceptable toxicities, or study closure whichever occurred first (up to 56 weeks)]

   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.

4. Cohort 1 - Duration of Response [time of response to progressive disease, death, unacceptable toxicities, or study closure whichever occurred first (up to 56 weeks)]

   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.

5. Cohort 2 - 3-month PSA Level Decline of Greater Than or Equal to 30% [baseline to 3 months]

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

6. Cohort 2 - PSA Velocity [baseline, 2 months and 3 months]

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

7. Cohort 2 - Number of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate) [baseline to first occurrence of tumor progression, skeletal event, symptomatic progression, or death (up to 31.3 months)]

   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.

8. Cohort 2 - Percentage of Participants With Progression Free Survival (PFS) at 6 Months and 12 Months [6 months and 12 months]

   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.

9. Cohort 2 - Overall Survival [baseline to date of death from any cause (up to 69.6 weeks)]

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

10. Cohort 2 - Duration of Response [time of response to first occurrence of tumor progression, skeletal event, symptomatic progression, or death (up to 31.3 months)]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• You are expected to be alive in the 12 weeks.

• You are at least 18 years old.

• You live close enough to the doctor's office to attend all of your required visits.

• You have not been treated with chemotherapy for your prostate cancer (cohort 1).

• Must have evidence of androgen-independent PSA-progressive disease without a history of or current (as judged by the investigator) clinical or radiographic evidence of metastatic disease with castrate levels of testosterone (<50 ng/dL) maintained by luteinizing hormone-releasing hormone (LHRH) agonist or bilateral orchiectomy following standard anti-androgen withdrawal. NOTE: PSA progression is defined as have rising PSA values of <=5 ng/mL (at least 3 measurements 1 week apart) with castrate levels of testosterone <50 ng/dL following appropriate antiandrogen withdrawal, without evidence of metastases. (cohort 1)

• No prior systemic chemotherapy for prostate cancer. No prior chemotherapy for any other indication within 2 years of study entry. NOTE: Participants previously treated with chemotherapy in the adjuvant/neoadjuvant setting were not be eligible. (cohort 1)

• You have had one prior docetaxel-based chemotherapy regimen (cohort 2).

• You have evidence of metastatic prostate cancer with bone or soft tissue disease (cohort 2).

• Must have evidence of docetaxel-resistant, androgen-independent metastatic prostate cancer with bone or soft tissue disease (PSA only participants are not eligible) defined as either: clinical, PSA or radiographic disease progression while receiving docetaxel-based therapy or PSA and/or radiographic progression at any time after completion of a docetaxel-containing regimen with PSA progression defined as a 25% increase in PSA from the post docetaxel value or interval progression in known metastatic sites of disease or development of new sites of disease on bone scan or computed tomography (CT) imaging. Note: Participants who discontinued a docetaxel-containing regimen due to toxicity or any other reasons not related to disease progression while on treatment, and were not able to complete at least 2 cycles, were not be eligible. (cohort 2)

• Your organs must be functioning properly.

Exclusion Criteria:

• You are unable to swallow pills.

• You have another illness besides your prostate cancer.

• You have taken another experimental drug within the last 30 days.

• You have a serious heart condition.

• You are receiving another anti-cancer therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Los Angeles	California	United States	90025
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Stanford	California	United States	94305
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	New Haven	Connecticut	United States	06520
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ann Arbor	Michigan	United States	48109
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Las Vegas	Nevada	United States	89135
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Buffalo	New York	United States	14263
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	New York	New York	United States	10032
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cleveland	Ohio	United States	44195
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lancaster	Pennsylvania	United States	17605
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Memphis	Tennessee	United States	38120
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Lilly Clinical Trial Registry

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00428714
• Other Study ID Numbers: 10737; H6Q-MC-S024
• First Posted: Jan 30, 2007
• Last Update Posted: Nov 25, 2020
• Last Verified: Nov 1, 2020

• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Pre-assignment Detail	Table presents reason for treatment discontinuation.

Arm/Group Title	Enzastaurin-Cohort 1	Enzastaurin-Cohort 2
Arm/Group Description	Chemo-naive participants who had androgen-independent prostate cancer with rising PSA levels but no clinical or radiographic evidence of metastatic disease. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.	Participants with progressed, metastatic prostate cancer who had received prior treatment with a docetaxel-containing agent. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.
Period Title: Overall Study
STARTED	31	42
Received at Least 1 Dose of Study Drug	31	42
COMPLETED	0	0
NOT COMPLETED	31	42

Baseline Characteristics

Arm/Group Title	Enzastaurin-Cohort 1	Enzastaurin-Cohort 2	Total
Arm/Group Description	Chemo-naive participants who had androgen-independent prostate cancer with rising PSA levels but no clinical or radiographic evidence of metastatic disease. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.	Participants with progressed, metastatic prostate cancer who had received prior treatment with a docetaxel-containing agent. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.	Total of all reporting groups
Overall Participants	31	42	73
Age (Years) [Mean (Standard Deviation) ]
Age	72.2 (10.0)	69.9 (7.77)	70.88 (9.90)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	31 100%	42 100%	73 100%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	27 87.1%	39 92.9%	66 90.4%
African	3 9.7%	0 0%	3 4.1%
Hispanic	1 3.2%	1 2.4%	2 2.7%
East Asian	0 0%	1 2.4%	1 1.4%
West Asian	0 0%	1 2.4%	1 1.4%
Region of Enrollment (Count of Participants)
United States	31 100%	42 100%	73 100%
Eastern Cooperative Oncology Group Scale Performance Status (ECOG) (Count of Participants)
0	22 71%	14 33.3%	36 49.3%
1	9 29%	26 61.9%	35 47.9%
2	0 0%	2 4.8%	2 2.7%

Outcome Measures

1. Primary Outcome

Title	Cohort 1 - Number of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate)
Description	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Enzastaurin-Cohort 1
Arm/Group Description	Chemo-naive participants who had androgen-independent prostate cancer with rising PSA levels but no clinical or radiographic evidence of metastatic disease. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.
Measure Participants	27
Number [Participants]	1 3.2%

2. Primary Outcome

Title	Cohort 2 - Progression-free Survival (PFS)-Overall
Description	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Enzastaurin-Cohort 2
Arm/Group Description	Participants with progressed, metastatic prostate cancer who had received prior treatment with a docetaxel-containing agent. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.
Measure Participants	42
Median (90% Confidence Interval) [Weeks]	11.0

3. Secondary Outcome

Title	Cohort 1 - Number of Participants With a 3-month PSA Level Decline of Greater Than or Equal to 30%
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Enzastaurin-Cohort 1
Arm/Group Description	Chemo-naive participants who had androgen-independent prostate cancer with rising PSA levels but no clinical or radiographic evidence of metastatic disease. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.
Measure Participants	27
Number [participants]	1 3.2%

4. Secondary Outcome

Title	Cohort 1 - PSA Velocity
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	LY317615- Cohort 1
Arm/Group Description	Chemo-naive participants who had androgen-independent prostate cancer with rising PSA levels but no clinical or radiographic evidence of metastatic disease. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.
Measure Participants	27
PSA Velocity at 2 months	0.10003
PSA Velocity at 3 months	0.06289

5. Secondary Outcome

Title	Cohort 1 - Progression-free Survival (PFS)-Overall
Description	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Enzastaurin-Cohort 1
Arm/Group Description	Chemo-naive participants who had androgen-independent prostate cancer with rising PSA levels but no clinical or radiographic evidence of metastatic disease. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.
Measure Participants	27
Median (Full Range) [weeks]	12

6. Secondary Outcome

Title	Cohort 1 - Duration of Response
Description	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Enzastaurin-Cohort 1
Arm/Group Description	Chemo-naive participants who had androgen-independent prostate cancer with rising PSA levels but no clinical or radiographic evidence of metastatic disease. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.
Measure Participants	1
Median (95% Confidence Interval) [weeks]	27.9

7. Secondary Outcome

Title	Cohort 2 - 3-month PSA Level Decline of Greater Than or Equal to 30%
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Enzastaurin-Cohort 2
Arm/Group Description	Participants with progressed, metastatic prostate cancer who had received prior treatment with a docetaxel-containing agent. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.
Measure Participants	42
Number [participants]	0 0%

8. Secondary Outcome

Title	Cohort 2 - PSA Velocity
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Enzastaurin-Cohort 2
Arm/Group Description	Participants with progressed, metastatic prostate cancer who had received prior treatment with a docetaxel-containing agent. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.
Measure Participants	40
PSA Velocity at 2 months	0.30297
PSA Velocity at 3 months	0.26702

9. Secondary Outcome

Title	Cohort 2 - Number of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate)
Description	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Enzastaurin-Cohort 2
Arm/Group Description	Participants with progressed, metastatic prostate cancer who had received prior treatment with a docetaxel-containing agent. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.
Measure Participants	42
Number [participants]	0 0%

10. Secondary Outcome

Title	Cohort 2 - Percentage of Participants With Progression Free Survival (PFS) at 6 Months and 12 Months
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Enzastaurin-Cohort 2
Arm/Group Description	Participants with progressed, metastatic prostate cancer who had received prior treatment with a docetaxel-containing agent. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.
Measure Participants	42
6 month PFS rate	3.0 9.7%
12 month PFS rate	0.0 0%

11. Secondary Outcome

Title	Cohort 2 - Overall Survival
Description	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Enzastaurin-Cohort 2
Arm/Group Description	Participants with progressed, metastatic prostate cancer who had received prior treatment with a docetaxel-containing agent. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.
Measure Participants	42
Median (Full Range) [weeks]	NA

12. Secondary Outcome

Title	Cohort 2 - Duration of Response
Description	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Enzastaurin-Cohort 2
Arm/Group Description	Participants with progressed, metastatic prostate cancer who had received prior treatment with a docetaxel-containing agent. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.
Measure Participants	0

Adverse Events

Arm/Group Title	Enzastaurin-Cohort 1		Enzastaurin-Cohort 2
Arm/Group Description	Chemo-naive participants who had androgen-independent prostate cancer with rising PSA levels but no clinical or radiographic evidence of metastatic disease. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.		Participants with progressed, metastatic prostate cancer who had received prior treatment with a docetaxel-containing agent. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.
All Cause Mortality
	Enzastaurin-Cohort 1		Enzastaurin-Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Enzastaurin-Cohort 1		Enzastaurin-Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/31 (6.5%)		12/42 (28.6%)
Cardiac disorders
Atrial fibrillation	1/31 (3.2%)	1	0/42 (0%)	0
Cardiac failure congestive	1/31 (3.2%)	1	0/42 (0%)	0
Gastrointestinal disorders
Abdominal pain upper	0/31 (0%)	0	1/42 (2.4%)	1
Colitis	0/31 (0%)	0	1/42 (2.4%)	1
Constipation	0/31 (0%)	0	1/42 (2.4%)	1
Diarrhoea	0/31 (0%)	0	1/42 (2.4%)	1
Nausea	0/31 (0%)	0	1/42 (2.4%)	1
Rectal haemorrhage	0/31 (0%)	0	1/42 (2.4%)	1
Vomiting	0/31 (0%)	0	2/42 (4.8%)	2
General disorders
Fatigue	0/31 (0%)	0	1/42 (2.4%)	1
Oedema peripheral	0/31 (0%)	0	1/42 (2.4%)	1
Pyrexia	0/31 (0%)	0	1/42 (2.4%)	1
Infections and infestations
Campylobacter infection	0/31 (0%)	0	1/42 (2.4%)	1
Pneumonia	1/31 (3.2%)	1	0/42 (0%)	0
Investigations
Blood creatine increased	0/31 (0%)	0	2/42 (4.8%)	2
Blood creatinine increased	0/31 (0%)	0	2/42 (4.8%)	2
International normalised ratio increased	0/31 (0%)	0	1/42 (2.4%)	1
Prothrombin time prolonged	0/31 (0%)	0	1/42 (2.4%)	1
Metabolism and nutrition disorders
Dehydration	0/31 (0%)	0	2/42 (4.8%)	2
Hyperkalaemia	0/31 (0%)	0	1/42 (2.4%)	1
Musculoskeletal and connective tissue disorders
Bone pain	0/31 (0%)	0	1/42 (2.4%)	1
Muscular weakness	0/31 (0%)	0	2/42 (4.8%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	1/31 (3.2%)	1	0/42 (0%)	0
Nervous system disorders
Spinal cord compression	0/31 (0%)	0	2/42 (4.8%)	2
Renal and urinary disorders
Bladder obstruction	0/31 (0%)	0	1/42 (2.4%)	1
Haematuria	0/31 (0%)	0	1/42 (2.4%)	1
Hydronephrosis	0/31 (0%)	0	1/42 (2.4%)	1
Micturition urgency	0/31 (0%)	0	1/42 (2.4%)	1
Renal failure	1/31 (3.2%)	1	0/42 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	1/31 (3.2%)	1	0/42 (0%)	0
Dyspnoea	1/31 (3.2%)	1	0/42 (0%)	0
Nasal congestion	1/31 (3.2%)	1	0/42 (0%)	0
Pulmonary embolism	0/31 (0%)	0	1/42 (2.4%)	1
Vascular disorders
Hypotension	0/31 (0%)	0	1/42 (2.4%)	1
Urinary bladder haemorrhage	0/31 (0%)	0	1/42 (2.4%)	1
Other (Not Including Serious) Adverse Events
	Enzastaurin-Cohort 1		Enzastaurin-Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/31 (93.5%)		42/42 (100%)
Blood and lymphatic system disorders
Anaemia	3/31 (9.7%)	4	2/42 (4.8%)	2
Lymphopenia	2/31 (6.5%)	3	1/42 (2.4%)	1
Gastrointestinal disorders
Constipation	2/31 (6.5%)	2	6/42 (14.3%)	7
Diarrhoea	9/31 (29%)	13	6/42 (14.3%)	7
Dry mouth	3/31 (9.7%)	3	0/42 (0%)	0
Flatulence	2/31 (6.5%)	2	1/42 (2.4%)	1
Nausea	5/31 (16.1%)	5	13/42 (31%)	13
Rectal haemorrhage	2/31 (6.5%)	2	1/42 (2.4%)	1
Vomiting	0/31 (0%)	0	7/42 (16.7%)	7
General disorders
Fatigue	12/31 (38.7%)	13	17/42 (40.5%)	18
Oedema	0/31 (0%)	0	6/42 (14.3%)	6
Oedema peripheral	4/31 (12.9%)	4	5/42 (11.9%)	6
Pain	2/31 (6.5%)	2	4/42 (9.5%)	4
Pyrexia	0/31 (0%)	0	4/42 (9.5%)	4
Infections and infestations
Upper respiratory tract infection	2/31 (6.5%)	2	0/42 (0%)	0
Investigations
Alanine aminotransferase increased	2/31 (6.5%)	2	1/42 (2.4%)	1
Aspartate aminotransferase increased	3/31 (9.7%)	3	2/42 (4.8%)	2
Blood creatinine increased	2/31 (6.5%)	2	3/42 (7.1%)	3
Haemoglobin decreased	0/31 (0%)	0	3/42 (7.1%)	3
Urine colour abnormal	11/31 (35.5%)	11	2/42 (4.8%)	2
Weight decreased	0/31 (0%)	0	7/42 (16.7%)	7
Metabolism and nutrition disorders
Anorexia	0/31 (0%)	0	12/42 (28.6%)	14
Decreased appetite	1/31 (3.2%)	1	4/42 (9.5%)	4
Dehydration	0/31 (0%)	0	4/42 (9.5%)	4
Hypocholesterolaemia	2/31 (6.5%)	2	0/42 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/31 (3.2%)	1	5/42 (11.9%)	6
Back pain	3/31 (9.7%)	3	7/42 (16.7%)	7
Bone pain	0/31 (0%)	0	7/42 (16.7%)	8
Muscle spasms	2/31 (6.5%)	2	0/42 (0%)	0
Muscular weakness	2/31 (6.5%)	2	2/42 (4.8%)	2
Pain in extremity	1/31 (3.2%)	1	9/42 (21.4%)	11
Nervous system disorders
Headache	2/31 (6.5%)	2	1/42 (2.4%)	1
Psychiatric disorders
Insomnia	4/31 (12.9%)	5	3/42 (7.1%)	3
Reproductive system and breast disorders
Erectile dysfunction	0/31 (0%)	0	4/42 (9.5%)	4
Respiratory, thoracic and mediastinal disorders
Cough	2/31 (6.5%)	2	3/42 (7.1%)	3
Dyspnoea	0/31 (0%)	0	3/42 (7.1%)	3
Vascular disorders
Hot flush	1/31 (3.2%)	1	3/42 (7.1%)	3
Hypertension	2/31 (6.5%)	2	1/42 (2.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.