title: A phase II, single-arm study of the anti-α5β1 integrin antibody volociximab as monotherapy in patients with platinum-resistant advanced epithelial ovarian or primary peritoneal cancer.
abstract: OBJECTIVE
  This phase II, multicenter, single-arm, two-stage study in platinum-resistant, advanced epithelial ovarian or primary peritoneal cancer evaluated the efficacy, safety, and tolerability of weekly single-agent volociximab. Pharmacokinetic/pharmacodynamic (PK/PD) studies were also performed.
  
  
  METHODS
  Sixteen patients were enrolled in Stage 1. Volociximab was administered at 15mg/kg IV qwk until progression of disease or drug intolerability. Tumor response was assessed every 8weeks. Serum samples for PK or whole blood for the evaluation of circulating tumor cells, endothelial cells, and endothelial progenitor cells were obtained on Days 1, 8, 15, 29, and 50. Ascites from one patient was collected for volociximab concentration analysis. Archived tumor tissue was analyzed by immunohistochemistry (IHC) for α5 integrin expression.
  
  
  RESULTS
  Safety data are available on all 16 patients; 14 were evaluable for efficacy. One patient had stable disease at 8weeks. The remaining 13 progressed on treatment. Twelve patients (75%) experienced study-related adverse events (AEs); the most common (≥20%) were headache and fatigue. Three patients experienced possible study-related serious AEs (SAEs): reversible posterior leukoencephalopathy syndrome, pulmonary embolism, and hyponatremia. Peak serum concentrations of volociximab increased 2-3 fold from Day 1 to Day 50. Clinically relevant trough levels were achieved (>150μg/mL). IHC analysis of archived tumor sections showed low-to-moderate expression of α5 integrin on all ovarian cancer tissue evaluated.
  
  
  CONCLUSIONS
  Despite insufficient clinical activity in this refractory patient population to continue the study, weekly volociximab was well tolerated, and the gained understanding of the mechanism of action of volociximab will inform future development efforts.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. bell-mck@mskcc.org
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Bell-McGuinn
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Matthews
authors.forename: Steffan N
authors.initials: SN
authors.lastname: Ho
authors.forename: Minal
authors.initials: M
authors.lastname: Barve
authors.forename: Lucy
authors.initials: L
authors.lastname: Gilbert
authors.forename: Richard T
authors.initials: RT
authors.lastname: Penson
authors.forename: Ernst
authors.initials: E
authors.lastname: Lengyel
authors.forename: Rameshraja
authors.initials: R
authors.lastname: Palaparthy
authors.forename: Kye
authors.initials: K
authors.lastname: Gilder
authors.forename: Artemios
authors.initials: A
authors.lastname: Vassos
authors.forename: William
authors.initials: W
authors.lastname: McAuliffe
authors.forename: Sara
authors.initials: S
authors.lastname: Weymer
authors.forename: Jeremy
authors.initials: J
authors.lastname: Barton
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Schilder
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D000077216:Carcinoma, Ovarian Epithelial; D019008:Drug Resistance, Neoplasm; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D039081:Integrin alpha5beta1 / Q000096:biosynthesis / Q000276:immunology; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000187:drug effects / Q000473:pathology; D009944:Organoplatinum Compounds / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013234:Stem Cells / Q000187:drug effects / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D039081:Integrin alpha5beta1; D009944:Organoplatinum Compounds; C516631:volociximab