title: A phase II study of saracatinib (AZD0530), a Src inhibitor, administered orally daily to patients with advanced thymic malignancies.
abstract: OBJECTIVE
  Thymic malignancies are rare, and options are limited for metastatic disease. Src plays a role in normal thymic epithelial maturation, and its inhibition with the oral compound saracatinib was postulated to be effective in controlling thymic malignancy.
  
  
  METHODS
  Patients with unresectable thymic malignancy were treated with saracatinib 175mg by mouth daily in 28 days cycles with radiographic evaluation at cycle 2 day 1 for safety, then cycle 3 day 1 and every 8 weeks thereafter. Response was evaluated by RECIST 1.0. A two-stage optimal design was used, powered to detect a true response rate of 20%.
  
  
  RESULTS
  21 patients were enrolled at two institutions, 12 of them with thymoma, 9 with thymic carcinoma. Thymoma patients received a median of 4.5 cycles and thymic carcinoma patients a median of 1 cycle. There were no responses, so accrual was halted after the first stage per protocol. 9 patients had stable disease beyond the first assessment. Median time to progression was 5.7 months for thymoma patients and 3.6 months for thymic carcinoma patients. Saracatinib was well tolerated.
  
  
  CONCLUSIONS
  Src inhibition by saracatinib did not produce any radiographic responses, though some patients did experience stable disease. Though negative, this study shows the feasibility of completing a trial in this rare disease, and of accruing reasonably significant numbers of thymic carcinoma patients. More clinical trials are required for this population (NCT00718809).
authors.affiliation: University of California, San Francisco, CA, United States. Electronic address: matthew.gubens@ucsf.edu.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Gubens
authors.affiliation: Indiana University, Indianapolis, IN, United States.
authors.forename: Matthew
authors.initials: M
authors.lastname: Burns
authors.affiliation: Indiana University, Indianapolis, IN, United States.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Perkins
authors.affiliation: Stanford University, Stanford, CA, United States.
authors.forename: Melanie San
authors.initials: MS
authors.lastname: Pedro-Salcedo
authors.affiliation: Indiana University, Indianapolis, IN, United States.
authors.forename: Sandy K
authors.initials: SK
authors.lastname: Althouse
authors.affiliation: Indiana University, Indianapolis, IN, United States.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Loehrer
authors.affiliation: Stanford University, Stanford, CA, United States.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Wakelee
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D052117:Benzodioxoles / Q000008:administration & dosage* / Q000009:adverse effects; D002277:Carcinoma / Q000000981:diagnostic imaging / Q000188:drug therapy*; D018450:Disease Progression; D018572:Disease-Free Survival; D057239:Early Termination of Clinical Trials; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D011859:Radiography; D066066:Response Evaluation Criteria in Solid Tumors; D015996:Survival Rate; D013945:Thymoma / Q000000981:diagnostic imaging / Q000188:drug therapy*; D013953:Thymus Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D017211:Treatment Failure; D055815:Young Adult; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D052117:Benzodioxoles; D011799:Quinazolines; C515233:saracatinib; D019061:src-Family Kinases
keywords: AZD0530; Saracatinib; Src inhibition; Thymic carcinoma; Thymoma