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This Phase 2 clinical trial was designed to estimate objective response rates, or tumor shrinkage, in patients with advanced breast cancer when treated with weekly custirsen in combination with docetaxel chemotherapy. Secondary objectives include: (a) determining the tolerability and toxicity of custirsen in combination with docetaxel chemotherapy, (b) describing time to progression, (c) describing overall survival, and (d) measuring evidence of custirsen effect on serum clusterin levels. This clinical trial was a multi center trial conducted at centers in Canada in 15 patients. A further 27 patients were contemplated in the event that six or more of the first 15 patients achieved tumor shrinkage equal to or greater than 30% from baseline tumor size. Since 5 patients achieved tumor shrinkage greater than 30%, this trial completed enrollment at 15 patients. The results of the treatment with custirsen on these patients' serum clusterin levels and survival are pending.
This clinical trial was conducted under the management of the National Cancer Institute of Canada-Clinical Trials Group (NCIC-CTG) at multiple Canadian sites. Dr. Stephen Chia and his colleagues presented the results of this study at the American Association for Cancer Research 2007 Annual Meeting.
As of April 2007, median progression-free survival was 8 months. Median overall survival has not yet been reached, but is expected to exceed 11 months.
The following table summarizes the response to therapy for measurable disease:
| Response to Treatment |
% of Patients |
Disease Control
(CR+PR+SD) |
93% |
| Complete Response |
0% |
| Partial Response |
33% |
Stable Disease
(Duration) |
60%
(9.3 months) |
| Progressive Disease |
7% |
| Inevaluable |
0% |
These data are consistent with our pre-clinical data with secondary chemotherapies and preliminary data from our Phase 1 clinical trials which indicate that custirsen treatment may increase the number of patients with disease stabilization and may improve survival without necessarily increasing the number of patients with greater than 30% tumor shrinkage.
Patients in this clinical trial experienced various adverse events, the majority of which are known to be associated with docetaxel chemotherapy and the disease. The majority of the events were mild. The most common events were fatigue, fever, rigors and chills, flu-like syndrome, hair loss, weight loss, diarrhea, nausea, vomiting, inflammation of the lining of the digestive tract, taste alteration, sensory nerve pain and joint pain. Decreased white blood cell counts and anemia were also observed. Four (4) patients out of the 15 treated in this clinical trial, experienced serious adverse events. All of the serious adverse events were attributed to the chemotherapy or disease, except for one case of fever with a reduced number of cells of a specific white blood cell type which was possibly related to the combination of custirsen and the chemotherapeutic agent.
It is anticipated that additional follow-up data from the 15 patients in this clinical trial will be available by mid-2008.
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