Phase I Trial of DNA Methyltransferase Inhibitor Guadecitabine Combined with Cisplatin and Gemcitabine for Solid Malignancies Including Urothelial Carcinoma (SPIRE).

ABSTRACT:

Purpose

Preclinical data indicate that DNA methyltransferase inhibition will circumvent cisplatin resistance in various cancers.

Patient and methods

SPIRE comprised a dose-escalation phase for incurable metastatic solid cancers, followed by a randomized dose expansion phase for neoadjuvant treatment of T2-4a N0 M0 bladder urothelial carcinoma. The primary objective was a recommended phase II dose (RP2D) for guadecitabine combined with gemcitabine and cisplatin. Treatment comprised 21-day gemcitabine and cisplatin cycles (cisplatin 70 mg/m², i.v., day 8 and gemcitabine 1,000 mg/m², i.v., days 8 + 15). Guadecitabine was injected subcutaneously on days 1-5, within escalation phase cohorts, and to half of 20 patients in the expansion phase. Registration ID:

SUBMITTER: Crabb SJ 

PROVIDER: S-EPMC7611191 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature