title: Phase II trial of OGX-011 in combination with docetaxel in metastatic breast cancer.
abstract: OBJECTIVE
  Clusterin is an antiapoptotic protein activated in response to cellular stress. OGX-011 is a second-generation antisense oligonucleotide that inhibits clusterin expression. The primary objective of this phase II trial was to assess the safety and efficacy of the combination of OGX-011 and docetaxel for metastatic breast cancer.
  
  
  METHODS
  Women with measurable metastatic breast cancer and <or=1 chemotherapy regimen were eligible. Three loading doses of OGX-011 640 mg i.v. followed by weekly OGX-011 and docetaxel 75 mg/m(2) (every 3 weeks) were given. A two-stage design was used with a hypothesis of H(0) <or=35% and H(a) >or=55%. Objective response in >or=6 of the first 14 patients was required for the trial to continue to the second stage.
  
  
  RESULTS
  Fifteen patients were enrolled. A median of six cycles were delivered (range, 2-10). Five partial responses were confirmed for a 33% response rate (95% confidence interval, 11.8-61.6%) with a further 9 (60%) patients showing stable disease. The median duration of stable disease was 9.3 months. The median time to progression was 8 months (95% confidence interval, 5.62-9.43 months). Toxic effects were similar to those with single agent docetaxel. Although serum clusterin decreased on treatment, there was no relationship observed between the magnitude of decrease and response.
  
  
  CONCLUSIONS
  The combination of OGX-011 and docetaxel at 75 mg/m(2) is well tolerated and clinical activity was seen in these patients with metastatic breast cancer, but there was an insufficient number of responses to meet the criteria for proceeding to the second stage of accrual.
authors.affiliation: Division of Medical Oncology, British Columbia Cancer Agency, University of British Columbia, 600 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 4E6. schia@bccancer.bc.ca
authors.forename: Stephen
authors.initials: S
authors.lastname: Chia
authors.forename: Susan
authors.initials: S
authors.lastname: Dent
authors.forename: Susan
authors.initials: S
authors.lastname: Ellard
authors.forename: Peter M
authors.initials: PM
authors.lastname: Ellis
authors.forename: Ted
authors.initials: T
authors.lastname: Vandenberg
authors.forename: Karen
authors.initials: K
authors.lastname: Gelmon
authors.forename: Jean
authors.initials: J
authors.lastname: Powers
authors.forename: Wendy
authors.initials: W
authors.lastname: Walsh
authors.forename: Lesley
authors.initials: L
authors.lastname: Seymour
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Eisenhauer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy*; D051152:Clusterin / Q000097:blood* / Q000737:chemistry; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D043823:Taxoids / Q000008:administration & dosage*; D013873:Thionucleotides / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D051152:Clusterin; C503781:OGX-011; D016376:Oligonucleotides, Antisense; D043823:Taxoids; D013873:Thionucleotides; D000077143:Docetaxel