Primary Outcome Measures:
- • To determine the maximum tolerated dose (MTD) of OGX-427 when administered as a single agent, up to a 1000 mg dose level. [ Time Frame: approximately 2 years ] [ Designated as safety issue: Yes ]
- • To further evaluate the safety profile at one dose level below the MTD derived for OGX-427 administered as a single agent and at the MTD level when OGX 427 is administered in combination with a taxane chemotherapy (docetaxel). [ Time Frame: approximately 2 years ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- To determine the pharmacokinetic profile of OGX-427 when used as a single agent and when used in combination with a taxane. [ Time Frame: approximately 2 years ] [ Designated as safety issue: Yes ]
- To determine whether OGX-427 alone or when co-administered with a taxane alters ECG intervals and morphology. [ Time Frame: approximately 2 years ] [ Designated as safety issue: Yes ]
- To document objective responses and disease stabilization when OGX-427 is administered either alone or in combination with a taxane. [ Time Frame: approximately 2 years ] [ Designated as safety issue: Yes ]
- To assess for a biologically effective dose(s) of OGX-427 that inhibits Hsp27 and other related protein levels in patient's serum. [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]
- To assess for a biologically effective dose(s) of OGX-427 when used as a single agent that reduces serum PSA levels in patients with HRPC. [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]
- To estimate a biological dose with an acceptable toxicity profile for further evaluation in Phase 2 studies [ Time Frame: approximately 2 years ] [ Designated as safety issue: Yes ]
This study is for patients with breast, prostate, ovarian, non-small cell lung (NSCL) or bladder cancer who have failed potentially curative treatments or for whose disease a curative treatment does not exist.
OGX-427 is a second-generation ASO that inhibits expression of Hsp27. Hsp27 is one of the heat shock proteins. Hsp27 increases with cell stress, including cytotoxic chemotherapy, radiation therapy and hormone therapy and has been shown to inhibit cell death. Thus, decreasing Hsp27 as a cancer therapy is attractive as a therapy as it should result in down regulation of pathways implicated in cancer progression and development of resistance to treatment.
A number of in vitro and in vivo pharmacological studies have demonstrated that OGX-427 has single-agent activity in reducing Hsp27, inhibiting cell growth and inducing cell death in several human cancer cell lines. OGX-427 has also demonstrated chemosensitizing activity in studies using cell lines and animal models in combination with several cytotoxic drugs, including docetaxel.
Docetaxel (Taxotere®) has anticancer activity in breast, prostate, ovarian, non-small cell lung and bladder cancer. Docetaxel has been approved by Health Canada and the Food and Drug Administration for the treatment of patients with breast, prostate, ovarian and non-small cell lung cancer.