A Phase 2 Trial of Protein Kinase C Iota Inhibition With the Combination of Auranofin and Sirolimus in Patients With Recurrent Ovarian Cancer.

OBJECTIVES

This trial served as a proof-of-concept for whether inhibition of protein kinase C iota (PKCι) with auranofin and sirolimus provide antineoplastic effects in patients with recurrent high-grade serous ovarian cancer.

METHODS

This drug combination was administered to patients with recurrent high-grade serous ovarian cancer. Dosing was based on unpublished phase 1 data and consisted of auranofin 6 mg and sirolimus 5 mg both orally per day of a 28-day cycle. The primary endpoint was tumor response. Available tumor tissue was assessed for PKCι protein expression by immunohistochemistry (IHC) and PRKCI copy number by fluorescence in-situ hybridization (FISH) after the start of cancer therapy.

RESULTS

Twenty-two patients were enrolled, and 21 were evaluable for all clinical trial endpoints. One patient was unevaluable because she did not receive a full chemotherapy cycle. No tumor responses were seen in the first 21 patients, resulting in early trial termination per a priori trial design. The median progression-free survival was 2.1 months (95% CI: 1.8-3.7). The median overall survival was 4.4 months (95% CI: 2.6-12.5). Fourteen (67%) patients had at least one grade 3 or worse adverse event. Nineteen of 21 evaluable patients had available tumor tissue, which showed the median PKCι copy number averaged per cell of 3 (range: 2 to 7), and PKCι expression (at least 1+) in all.

CONCLUSIONS

As prescribed here, auranofin and sirolimus manifested no antineoplastic activity in patients with recurrent high-grade serous ovarian cancer that expressed PKCι.