SAPROCAN: Saracatinib (AZD0530) and docetaxel in metastatic,castrate-refractory prostate cancer (mCRPC)—A phase I/randomized phase II study by the United Kingdom National Cancer Research Institute Prostate Group.

• DOI: 10.1200/jco.2021.39.6_suppl.107
• Publication Date: 2021-03-02T17:06:00Z
• Authors: Robert J. Jones; Amit Bahl; Johann S. De Bono; Christy Ralph; Tony Elliott; Angus Robinson; Charlotte Westbury; Alison Jane Birtle; John Nicholas Sta...; Andrew Protheroe; Balaji Venugopal; Fiona Thomson; Chantevy Pou; Karen Morris; Jonathan Tugwood; Laura Divers; Carol Hopkins; Elaine McCartney; Caroline Kelly; Simon J. Crabb
• Keywords: Tolerability; Clinical endpoint

107 Background: Saracatinib is an orally-available, highly selective inhibitor of Abl and Src family members. It ATP-competitive tyrosine kinase inhibitor. Preclinical data suggested that the combination a docetaxel synergistic, activity was also implicated in bone’s metabolic response to cancer metastases. Methods: Patients with mCRPC were initially enrolled open-label, dose escalation phase I trial oral saracatinib (cohorts 50mg, 125mg 175mg daily) (75mg/m 2 ) 3+3 design. Subsequent patients randomised 1:1 between placebo once daily. Pharmacokinetics (PK) explored exclude significant drug-drug interaction. The primary endpoint II biochemical or radiographic progression free survival (PFS). Secondary endpoints included overall (OS), safety tolerability. Changes circulating tumour cell (CTC) counts measured. designed 1-sided alpha 0.2 90% power detect hazard ratio (HR) for PFS 0.67. Results: 10 142 II. No limiting toxicities PK interactions observed recommended daily 75mg/m every 21 days. In II, HR 1.35 (80% confidence interval (CI) 1.07 1.70). OS 1.42 (1.08 – 1.81). 41/71 29/71 experienced treatment related grade 3 above arms respectively. 10/19 (53%) 14/27 (52%) evaluable demonstrated reduction CTCs from ≥5 < 5 /7.5ml blood at 6 weeks after starting Conclusions: Saracatinib, docetaxel, adds toxicity not efficacy mCRPC. This should be developed further Clinical information: ISRCTN22566729.