OGX-427 in Castration Resistant Prostate Cancer Patients
- Conditions
- Castration Resistant Prostate Cancer
- Interventions
- Drug: OGX-427Drug: Prednisone
- Registration Number
- NCT01120470
- Lead Sponsor
- British Columbia Cancer Agency
- Brief Summary
This study is being offered to patients who have castrate-resistant (also known as hormone-refractory) prostate cancer. The cancer has metastasized or spread outside the prostate area to other parts of the body or has recurred in the pelvic area after treatment.
The purpose of this clinical research study is to determine whether OGX-427 is able to slow the progression of prostate cancer and symptoms of disease when given with prednisone better than when prednisone is given alone in patients with prostate cancer whose disease has spread outside the prostate area.
Research Hypothesis:
That adding OGX-427 to prednisone treatment will produce a progression free rate of 20%.
- Detailed Description
Prostate cancer is the most common cancer diagnosed and the second most common cause of cancer death in men in North America.
Patients with metastatic disease have a poor prognosis, and although hormonal therapy in the form of medical or surgical castration can induce significant long-term remissions, development of androgen independent disease is inevitable. The current standard of care for CRPC is mainly palliative in its intent, and there are only limited proven treatment options which include: analgesia, radiation, bisphosphonates and chemotherapy such as mitoxantrone or docetaxel, with only the last treatment being associated with an overall survival benefit.
With the early commencement of androgen deprivation therapy and frequent use of PSA for monitoring disease progression, an increasing population of patients with CRPC is now being identified by a rising PSA rather than by new disease or symptoms. Early intervention with chemotherapy is of unknown benefit in these patients, and thus represents an appropriate group for phase II studies to evaluate novel agents with acceptable toxicity profiles.
Heat shock protein (Hsp) family members, including Hsp27, have attracted attention as new therapeutic targets for cancer. Hsp27 is a small, ATP-independent Hsp which is highly conserved across species. Hsp27 is expressed in prostate cancer and other malignancies. Expression of Hsp27 is induced by cell stress, including cytotoxic chemotherapy, radiation therapy, and hormone therapy. Overexpression of Hsp27 confers a resistant phenotype and is implicated in castration resistant progression of prostate cancer.
OGX 427 is a second generation antisense oligonucleotide (ASO) that inhibits expression of Hsp27. A number of in vitro and in vivo pharmacological studies have demonstrated that OGX 427 (or an Hsp27 ASO) has single-agent activity in reducing Hsp27 mRNA and protein, inhibiting cell proliferation, and inducing apoptosis in several human cancer cell lines. OGX 427 has also demonstrated chemosensitizing activity both in vitro and in vivo in combination with several cytotoxic drugs, including docetaxel. In an ongoing Phase I trial, OGX-427 has been administered as a single agent in doses from 200 to 1000 mg with weekly infusions occurring after a loading dose period of three infusions within the first 10 days of initiating treatment. OGX-427 treatment has been well tolerated, with the majority of the adverse events and laboratory toxicities reported being Grade 1 or Grade 2, although a symptom complex of rigors, pruritus, and erythema during or shortly after infusion of drug has required steroid prophylaxis and/or treatment in some patients at higher doses. No maximum tolerated dose has been identified based on toxicity. OGX 427 administration in combination with docetaxel is ongoing in the above-mentioned Phase 1 study.
Low dose corticosteroids have been shown to have some activity against prostate cancer with a beneficial effect on quality of life (QOL). Since chemotherapy for prostate cancer is palliative, low-dose prednisone has been used both as a single agent and added to chemotherapy regimens.
This Phase 2 study has been designed to evaluate the anti-tumor effects of OGX-427 plus low-dose prednisone versus low-dose prednisone alone in men with CRPC who have not previously received chemotherapy for metastatic or locally recurrent disease.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 74
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description OGX-427 and Prednisone OGX-427 OGX-427: Starting within 5 days of randomization, three loading doses at 600 mg IV within the first 10 days of initiating treatment, followed by weekly doses of 1000 mg IV Prednisone: 5 mg BID orally starting within 4 days following randomization and at least 24 hours prior to first loading dose of OGX-427 Prednisone Prednisone Control Arm: Prednisone: 5 mg BID orally starting within 4 days following randomization OGX-427 and Prednisone Prednisone OGX-427: Starting within 5 days of randomization, three loading doses at 600 mg IV within the first 10 days of initiating treatment, followed by weekly doses of 1000 mg IV Prednisone: 5 mg BID orally starting within 4 days following randomization and at least 24 hours prior to first loading dose of OGX-427
- Primary Outcome Measures
Name Time Method Disease Progression 12 weeks The primary efficacy endpoint is defined as the proportion of patients without disease progression at the 12-week evaluation after treatment with prednisone given with or without OGX-427.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (6)
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
BC Cancer Agency - Vancouver Centre
🇨🇦Vancouver, British Columbia, Canada
BC Cancer Agency - Centre for the Southern Interior
🇨🇦Kelowna, British Columbia, Canada
Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
University of Washington/Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada