Safety Study of an Antisense Product in Prostate, Ovarian, NSCL, Breast or Bladder Cancer
This study is for patients with cancer who have failed potentially curative treatments or for whose disease a curative treatment does not exist.
OGX-427 is an antisense product that inhibits expression of one of the heat shock proteins. Decreasing this heat shock protein (Hsp27) should result in down regulation of pathways implicated in cancer progression and development of resistance to treatment.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1 Study Evaluating A Second Generation Antisense Oligonucleotide (OGX 427) That Inhibits Heat Shock Protein 27 (Hsp27|
- • 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 ]
- • 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 ]
- 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 ]
- To determine whether OGX-427 alone or when co-administered with a taxane alters ECG intervals and morphology. [ Time Frame: approximately 2 years ]
- 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 ]
- 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 ]
- 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 ]
- To estimate a biological dose with an acceptable toxicity profile for further evaluation in Phase 2 studies [ Time Frame: approximately 2 years ]
|Study Start Date:||June 2007|
|Study Completion Date:||October 2011|
|Primary Completion Date:||June 2011 (Final data collection date for primary outcome measure)|
Each patient receives OGX-427
OGX-427 injection at 200mg, 400mg, 600mg, 800mg or 1000mg once a week until withdrawnDrug: Docetaxel
injection - 75 mg/M2 IV on Day 1 every 21 days for cohorts 6 & 7 only, together with appropriate dose of OGX-427 until withdrawn from study
Other Name: Taxotere
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00487786
|United States, Washington|
|Seattle Cancer Care Alliance|
|Seattle, Washington, United States, 98109|
|Canada, British Columbia|
|BC Cancer Agency|
|Vancouver, British Columbia, Canada, V5Z 4E6|
|Juravinski Cancer Center|
|Hamilton, Ontario, Canada, L8V 5C2|
|Principal Investigator:||Kim Chi, M.D.||University of British Columbia|