OncoGenex Technologies has announced data from a Phase II clinical trial of OGX-011 in combination with docetaxel in patients with metastatic breast cancer (MBC).
Data was presented by the National Cancer Institute of Canada - Clinical Trials Group at the American Association for Cancer Research 2007 Annual Meeting in Los Angeles, Calif.
- Of the 15 patients treated, five patients (33.3 percent) showed a partial response and nine patients (60 percent) showed disease stabilization
- Of the nine patients reported with stable disease, tumor reduction ranged from approximately eight to 28 percent and disease stabilization was sustained for a median of 9.3 months
- Only one patient advanced to progressive disease
- While patient monitoring is ongoing, the median progression free survival for all patients was eight months and the median time for survival has not yet been reached
- Clinical activity was seen for the combination of OGX-011 and docetaxel in this generally pre-treated group of patients with MBC, but did not meet the pre-determined criteria of six or more patients achieving tumour size reductions exceeding 30 percent required to expand the trial into a second stage of accrual
- Serum clusterin levels fell on treatment in most patients, and there was no statistical correlation between changes from baseline in clusterin levels and objective tumor response
"Taxanes represent an active class of chemotherapeutic agents currently used in the treatment of breast cancer, however the majority of patients will eventually develop resistance to the therapies," said Dr. Stephen Chia, Principal Investigator for this study and Medical Oncologist at the BC Cancer Agency. "The finding that all but one patient showed some degree of clinical benefit and the median duration of disease stabilization exceeded nine months is of interest in this small study."
"We are encouraged by the conclusion made by the investigators that the combination of OGX-011 and docetaxel has activity in this patient population and by the very low incidence of progressive disease," said Scott Cormack, president and CEO of OncoGenex. "As provided in our previous guidance, these data together with the data from our other Phase II programs in prostate cancer and non-small cell lung cancer, scheduled to be released later this year, will be considered in our planning for subsequent studies, including pivotal trials."
The primary objective of this study was to assess the objective response rates (reduction in tumor size) when OGX-011 is combined with docetaxel in patients with metastatic or locally recurrent breast cancer. Secondary endpoints included estimation of time to disease progression, overall survival and the effect of OGX-011 on serum clusterin.
Fifteen patients were enrolled and all were evaluable for toxicity and response. A median of six treatment cycles were delivered. Grade 3 adverse events commonly associated with chemotherapy alone included: fatigue (33 percent), vomiting (13 percent), edema (13 percent), arthralgias (13 percent) and dyspnea (13 percent). Five patients experienced febrile neutropenia. Investigators concluded that OGX-011 is well tolerated in combination with docetaxel.
Women with measurable metastatic breast cancer and no more than one previous chemotherapy regimen for MBC were eligible for this study. OGX-011 was delivered three times at 640 mg intravenously as a loading phase prior to initiating chemotherapy. The loading phase was followed by a weekly dose of 640 mg of OGX-011 in combination with 75 mg/m2 of docetaxel. Response was evaluated following every second cycle.
OGX-011 is designed to specifically inhibit the production of the cell-survival protein, clusterin. Clusterin production is associated with treatment resistance in many cancers and in response to various cancer treatments, including hormone ablation therapy, chemotherapy and radiation therapy. Preclinical studies have shown that inhibition of clusterin can disable the tumor cell's adaptive defences, render the tumor cells susceptible to attack with a variety of cancer therapies, including chemotherapy, and facilitate tumor cell death. OncoGenex is developing OGX-011 in collaboration with Isis Pharmaceuticals Inc.
The study was sponsored by the National Cancer Institute of Canada - Clinical Trials Group with support provided by OncoGenex Technologies Inc.