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

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.