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

Study Overview
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Brief Summary
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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

Official Title
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Phase 2 Trial Oral Enzastaurin in Prostate Cancer Patients Who Have Rising PSA (1) During Hormonal Manipulation and (2) After First-Line Cytotoxic Chemotherapy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: enzastaurin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enzastaurin-Cohort 1<br>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<br>* Administered orally<br>* Other names: LY317615;|
| Experimental: Enzastaurin-Cohort 2<br>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<br>* Administered orally<br>* Other names: LY317615;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1 - Number of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate) | 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. | Baseline to Measured Progressive Disease, Death, Unacceptable Toxicities, or Study Closure Whichever Occurred First (up to 56 weeks) | 
| Cohort 2 - Progression-free Survival (PFS)-Overall | 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. | baseline to first occurrence of tumor progression, skeletal event, symptomatic progression, or death (up to 31.3 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1 - Number of Participants With a 3-month PSA Level Decline of Greater Than or Equal to 30% | Number of participants exhibiting a PSA level decline from baseline of greater than or equal to 30% within the first 3 months of study. | baseline to 3 months | 
| Cohort 1 - PSA Velocity | PSA velocity is defined as the rate of change in the PSA level during the first 2 and 3 months of the study. | baseline, 2 months and 3 months | 
| Cohort 1 - Progression-free Survival (PFS)-Overall | 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. | baseline to date of disease progression, death, unacceptable toxicities, or study closure whichever occurred first (up to 56 weeks) | 
| Cohort 1 - Duration of Response | 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 of response to progressive disease, death, unacceptable toxicities, or study closure whichever occurred first (up to 56 weeks) | 
| Cohort 2 - 3-month PSA Level Decline of Greater Than or Equal to 30% | Number of participants exhibiting a PSA level decline from baseline of greater than or equal to 30% within the first 3 months of study. | baseline to 3 months | 
| Cohort 2 - PSA Velocity | PSA velocity is defined as the rate of change in the PSA level during the first 2 and 3 months of the study. | baseline, 2 months and 3 months | 
| Cohort 2 - Number of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate) | 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. | baseline to first occurrence of tumor progression, skeletal event, symptomatic progression, or death (up to 31.3 months) | 
| Cohort 2 - Percentage of Participants With Progression Free Survival (PFS) at 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. | 6 months and 12 months | 
| Cohort 2 - Overall Survival | Overall survival is the duration from enrollment to death. For participants who were alive, overall survival was censored at the last contact. | baseline to date of death from any cause (up to 69.6 weeks) | 
| Cohort 2 - Duration of Response | 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 of response to first occurrence of tumor progression, skeletal event, symptomatic progression, or death (up to 31.3 months) |