Saracatinib as a metastasis inhibitor in metastatic castration-resistant prostate cancer: A University of Chicago Phase 2 Consortium and DOD/PCF Prostate Cancer Clinical Trials Consortium Study

Edwin M. Posadas*, Rafi S. Ahmed, Theodore Karrison, Russell Z. Szmulewitz, Peter H. O'Donnell, James L. Wade, James Shen, Murali Gururajan, Margarit Sievert, Walter M. Stadler

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

BACKGROUND Fyn is a kinase that is upregulated in a subset of metastatic castration-resistant prostate cancer. Saracatinib potently inhibits Fyn activation. We have noted a relationship between Fyn expression and directional motility, a cellular process related to metastasis. As such we hypothesized that treatment with saracatinib would increase the time required to develop new metastatic lesions. METHODS Patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel were eligible for enrollment. This study was executed as a randomized discontinuation trial. During a lead-in phase of two 28-Day cycles, all patients received saracatinib. Afterward, patients with radiographically stable disease were randomized to either saracatinib or placebo. Patients continued treatment until evidence of new metastasis. RESULTS Thirty-one patients were treated. Only 26% of patients had stable disease after 8 weeks and thus proceeded to randomization. This required early termination of the study for futility. The 70% of patients who progressed after the lead-in phase exhibited expansion of existing lesions or decompensation due to clinical progression without new metastatic lesions. Fatigue was reported in more than 25% of patients (all grades) with only two patients experiencing grade 3 toxicity. Other grade 3 adverse events included dehydration, thrombocytopenia, and weakness. CONCLUSIONS This study was unable to determine if saracatinib had potential as metastasis inhibitor. Metastasis inhibition by saracatinib may still be viable in an earlier time in the disease history. Prostate 76:286-293, 2016.

Original languageEnglish (US)
Pages (from-to)286-293
Number of pages8
JournalProstate
Volume76
Issue number3
DOIs
StatePublished - Feb 15 2016

Keywords

  • Fyn
  • azd0530
  • castration-resistant
  • prostate cancer
  • saracatinib

ASJC Scopus subject areas

  • Oncology
  • Urology

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