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Study OGX-011-04 was a Phase 2 clinical trial in patients with localized prostate cancer designed to assess the effects of combined hormone ablation therapy and weekly treatment with custirsen (OGX-011) prior to surgical removal of the prostate gland. This clinical trial was a single-arm, single center trial managed by Dr. Kim Chi and his colleagues at the BCCA Cancer Center. Dr. Chi presented the preliminary results of this study at the 2008 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncologists.
Objectives of this study were to determine pathologic complete response (pCR) rate and evaluate the effects of custirsen treatment on the prostate prior to prostatectomy. Patients with localized prostate cancer and high-risk features were eligible for this study. LHRH agonist (hormone ablation) was given with weekly custirsen treatment for 12 weeks and prostatectomy performed within 14 days of the last dose of custirsen. Twenty-four patients were enrolled.
The concentration of custirsen in prostate tissue was determined. Custirsen concentration associated with biological activity (ie, decreased expression of the target, custirsen) was observed for more than 7 days post infusion.
Prostate tissues, lymph nodes, and serial samples of mononuclear cells and serum were assessed for biological activity relative to the expression of the target, clusterin. Inhibition of clusterin expression was observed when the results were compared to those results obtained in patients who did not receive custirsen. Using laser capture microdissection and QRT-PCR, mean clusterin mRNA was decreased by 61.3% compared to control (p=0.009). In addition, the mean apoptotic index was significantly higher for patients treated with custirsen compared to controls [(12.6% vs 7.6% for control (p=0.003)].
Dr. Chi concluded that although neoadjuvant treatment was not associated with pathologic complete responses, decreased expression of the target, clusterin, and an increase in the apoptotic index of prostate tumor cells was observed. He also concluded that weekly custirsen treatment is well tolerated. The group is continuing their analyses.
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