Table 1. Clinical Studies conducted related to CLU and Custirsen (OGX-011). Data obtained from ClinicalTrials.gov.
| Phase | Status | Study title | Clinical Trials.gov Locator | Cancer types | Interventions | Results |
|---|---|---|---|---|---|---|
| I | Completed | OGX-011 and Docetaxel in Treating Patients with Metastatic or Locally Recurrent Solid Tumors | NCT00471432 | Bladder cancer; Breast cancer; Kidney cancer; Lung cancer; Ovarian cancer; Prostate cancer; Unspecified adult solid tumor, protocol specific | Drug: custirsen sodium; Drug: docetaxel; Other: pharmacological study | • OGX-011 could be given at the full biologically effective single-agent dose of 640 mg with both docetaxel schedules |
| • OGX-011 AUC and C(max) increased proportionally with no apparent effect on docetaxel pharmacokinetics | ||||||
| • At the end of cycle 1, serum clusterin showed mean decreases of 34% and 38% (range, 15–99%) at the 640-mg dose levels | ||||||
| II | Completed | OGX-011 and Docetaxel in Treating Women with Locally Advanced or Metastatic Breast Cancer | NCT00258375 | Breast cancer | Drug: custirsen sodium; Drug: Docetaxel | • Fifteen patients were enrolled to assess the safety and efficacy of the combination of |
| • OGX-011and docetaxel for metastatic breast cancer | ||||||
| • A median of 6 cycles was delivered [2–10]. 5 PR were confirmed for a 33% RR (95% CI: 11.8–61.6%) with a further 8 subjects (53%) demonstrating stable disease of a median duration of 5.7 months (1.6–9.3 months) | ||||||
| • Correlative studies with serum clusterin levels and clusterin expression in the primary tumor are ongoing. | ||||||
| I | Completed | Hormone Therapy and OGX-011 Before Radical Prostatectomy in Treating Patients with Prostate Cancer | NCT00054106 | Prostate cancer | Drug: buserelin; Drug: custirsen sodium; Drug: flutamide; Procedure: conventional surgery; Procedure: neoadjuvant therapy | • The plasma half-life of OGX-011 was approximately 2–3 hours, and the area under the concentration versus time curve and CMAX increased proportionally with dose (Ptrend<0.001) |
| • OGX-011 in prostate tissue increased with dose (Ptrend<0.001) |
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| • Dose-dependent decreases in prostate cancer and lymph node clusterin expression were observed by polymerase chain reaction of greater than 90% (Ptrend=0.008 and Ptrend<0.001, respectively) and by immunohistochemistry (Ptrend<0.001 and Ptrend=0.01, respectively) | ||||||
| II | Completed | Evaluation of Safety and Feasibility of OGX-011 in Combination With 2nd-line Chemotherapy in Patients With HRPC | NCT00327340 | Prostate cancer | Drug: custirsen/docetaxel; Drug: custirsen/mitoxantrone | • Twenty patients treated with DPC received a median of 8 cycles; overall survival (OS) was 15.8 months. TTPP was 10.0 months; 10 of 13 (77%) evaluable patients had pain responses. Three of 13 (23%) evaluable patients had objective partial responses. PSA declines of 90% or more, 50% or more, and 30% or more occurred in 4 (20%), 8 (40%), and 11 (55%) patients, respectively |
| • Twenty-two patients treated with MPC received a median of 6 cycles; OS was 11.5 months. The median TTPP was 5.2 months; 6 of 13 (46%) evaluable patients had pain responses. No objective responses were observed. PSA declines of 50% or more and 30% or more occurred in 6 (27%) and 7 (32%) patients, respectively | ||||||
| • Low serum CLU levels during treatment showed superior survival for patients based on modeling with proportional hazard regression with a time-dependent covariate and different landmarks | ||||||
| I, II | Completed | A Study of OGX-011/Gemcitabine/Platinum-Based Regimen in Stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC) | NCT00138658 | Non-small cell lung cancer | Drug: custirsen sodium | • Overall response was 25 of 81 (31%; 95% CI: 21–42%) |
| • The 1- and 2-year survivals were 54% and 30%, respectively | ||||||
| • Custirsen treatment decreased serum CLU levels in 95% of patients evaluated. Patients who achieved a minimum median CLU level for the population of ≤38 μg/mL during treatment had a median survival of 27.1 compared with 16.1 months for patients who did not (P=0.02) |
PR, partial response; RR, response rate; CMAX, peak plasma concentration; DPC, docetaxel + prednisone + custirsen; TTPP, median time to pain progression; PSA, prostate-specific antigen; MPC, mitoxantrone + prednisone + custirsen.