title: Phase II study of saracatinib (AZD0530) in patients with previously treated metastatic colorectal cancer.
abstract: BACKGROUND
  Src has a critical role in tumor cell migration and invasion. Increased Src activity has been shown to correlate with disease progression and poor prognosis, suggesting Src could serve as a therapeutic target for kinase inhibition. Saracatinib (AZD0530) is a novel selective oral Src kinase inhibitor.
  
  
  METHODS
  Metastatic colorectal cancer patients who had received one prior treatment and had measurable disease were enrolled in this phase 2 study. Saracatinib was administered at 175 mg by mouth daily for 28 day cycles until dose-limiting toxicity or progression as determined by staging every 2 cycles. The primary endpoint was improvement in 4 month progression-free survival. Design of Thall, Simon, and Estey was used to monitor proportion of patients that were progression free at 4 months. The trial was opened with plan to enroll maximum of 35 patients, with futility assessment every 10 patients.
  
  
  RESULTS
  A total of 10 patients were enrolled between January and November 2007. Further enrollment was stopped due to futility. Median progression-free survival was 7.9 weeks, with all 10 patients showing disease progression following radiographic imaging. Median overall survival was 13.5 months. All patients were deceased by time of analysis. Observed adverse events were notable for a higher than expected number of patients with grade 3 hypophosphatemia (n = 5).
  
  
  CONCLUSIONS
  Saracatinib is a novel oral Src kinase inhibitor that was well tolerated but failed to meet its primary endpoint of improvement in 4 month progression-free survival as a single agent in previously treated metastatic colorectal cancer patients.
authors.affiliation: Hematology-Oncology Fellow, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 463, Houston, TX, 77030, USA, smreddy1@mdanderson.org.
authors.forename: S M
authors.initials: SM
authors.lastname: Reddy
authors.forename: S
authors.initials: S
authors.lastname: Kopetz
authors.forename: J
authors.initials: J
authors.lastname: Morris
authors.forename: N
authors.initials: N
authors.lastname: Parikh
authors.forename: W
authors.initials: W
authors.lastname: Qiao
authors.forename: M J
authors.initials: MJ
authors.lastname: Overman
authors.forename: D
authors.initials: D
authors.lastname: Fogelman
authors.forename: I
authors.initials: I
authors.lastname: Shureiqi
authors.forename: C
authors.initials: C
authors.lastname: Jacobs
authors.forename: Z
authors.initials: Z
authors.lastname: Malik
authors.forename: C A
authors.initials: CA
authors.lastname: Jimenez
authors.forename: R A
authors.initials: RA
authors.lastname: Wolff
authors.forename: J L
authors.initials: JL
authors.lastname: Abbruzzese
authors.forename: G
authors.initials: G
authors.lastname: Gallick
authors.forename: C
authors.initials: C
authors.lastname: Eng
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D052117:Benzodioxoles / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D052117:Benzodioxoles; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C515233:saracatinib; D019061:src-Family Kinases