1. Reversing/re-engaging clinical platinum response through modulation of underlying mechanism:

Completed

• We have completed an imaging/translational trial using the AKT inhibitor oral GSK2141795 in platinum resistant ovarian cancer patients (NCT01266954, Gabra CI).
• We have completed a phase IB/II AKTRES (AKT inhibition in platinum resistant ovarian cancer) trial of carboplatin + taxol with AKT inhibitor GSK2110183 (Afuresertib) in platinum resistant patients (NCT01653912, Blagden CI).
• We completed a phase III OVATURE trial in platinum resistant ovarian cancer patients of weekly carboplatin +/- oral phenoxodiol (Gabra PI). 

ONGOING

• We have worked with Aprea to develop the PiSARRO trial (p53 Suppressor Activation in Recurrent High Grade Serous Ovarian Cancer NCT02098343, Green CI, Liverpool), a Phase Ib/II study of carboplatin and pegylated liposomal doxorubicin (PLD) with or without APR-246 - the phase IB has been completed and we have progressed into a randomised phase II trial.

We have also developed a EUTROC network-wide, academically led, research programme funded by Aprea, including several projects led from OCARC (Krell, Brown).

2. Tackling platinum resistance through other approaches:

COMPLETED

• We undertook a phase I/II trial ProGem2  of a gemcitabine pro-drug Nuc-1031 in recurrent ovarian cancer: 'Safety and Efficacy Study of Nuc-1031 and Carboplatin Combination to Treat Recurrent Ovarian Cancer' (Blagden PI). 

ONGOING

• We have developed the DICE trial (Dual TORC inhibition in clear cell and endometrioid carcinomas), a site of origin agnostic trial, based on observed synergy between MLN0128, the dual TORC inhibitor and paclitaxel, with Takeda Oncology - this has now evolved into two trials; DICE – Ovarian (in platinum resistant recurrent ovarian cancer, Gabra CI), due to open mid- 2017; and DICE – Uterine (a similar trial in uterine cancer, Gabra CI), opened in August 2016, and run across 78 international centres.