Hence, the SPIRE group out of the UK is running this phase 1b and randomized IIa trial to assess safety, dosing and biologic efficacy. They are co-administering a DNA methyltransferase inhibitor SGI-110 (guadecitabine) with standard gemcitabine and cisplatin chemotherapy (GC).
Study structure: (see pictures below)
- Dose escalation phase (initial)
- Followed by a randomized dose expansion phase
Target population:
- Patients with advanced/metastatic solid tumors, including bladder cancer
- GC as neoadjuvant treatment prior to cystectomy for bladder cancer (T2-4a N0 M0)
Primary objectives:
- To determine a recommended phase II dose (RP2D) of SGI-110 in combination with GC, using pre-defined dose limiting toxicity criteria assessed by CTCAE v4.03
- To determine a biologically effective dose based on serum DNA LINE-1 methylation and hemoglobin F re-expression status.
Dose Escalation Phase: Treatment comprises GC (Gemcitabine 1000 mg/m2, IVI, days 8 and 15; Cisplatin 70 mg/m2, IVI, day 8), and SGI-110 (subcutaneous, days 1-5) for up to 6 cycles of 21 days.
Up to 6 patients are enrolled in each of up to 4 SGI-110 dose level cohorts utilizing a ‘rolling 6’ design.
Dose Expansion Phase: 20 patients will be randomized 1:1 to GC, or GC + SGI-110 at the established RP2D, to expand safety and pharmacodynamic endpoint data.
SPIRE is coordinated by the CRUK Southampton Clinical Trials Unit and is currently recruiting to a 3rd dose escalation cohort through the UK Experimental Cancer Medicine Centre (ECMC) network. It was developed through the CRUK Combinations Alliance. Funding: Cancer Research UK (C9317/A19903) and Astex Pharmaceuticals. Sponsor: University Hospital Southampton NHS Foundation Trust.
Presented by: Simon J. Crabb, MD
Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA