191P - Phase II study of sodium valproate in combination with oral etoposide in platinum-resistant ovarian cancer

Background

Platinum-resistant ovarian cancer (PROC) is an unmet need. Oral etoposide is an active agent in PROC with response rates of around 20%. Sodium valproic acid (VPA) is a short-chain fatty acid histone deacetylase (HDAC) inhibitor that showed promising results as an anti-tumour agent in preclinical studies in PROC. We repurposed VPA in combination with oral etoposide to evaluate its efficacy.

Methods

In this prospective, single-arm, open-label, phase 2 study, we included patients ≥18 years with histologically or cytologically confirmed PROC and Eastern Cooperative Oncology Group performance status (ECOG-PS) 0-3. Patients received oral etoposide and oral VPA as 21- day cycles. Serum samples were collected from all participants to assess peak VPA drug levels. The primary endpoint was overall response rate (ORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity.

Results

27 patients were enrolled in the study, and 18 were included in the final analysis. The median age was 52 (45-59) years. Serous was the most common type 17 (94%). The median number of prior lines of treatment was 2 (1-3). ORR was 0% according to GCIG criteria. The disease was stable in two patients at four months with a clinical benefit rate (CBR) of 11%. The median OS and median PFS were seven months and two months, respectively. Grade >3 adverse events were reported in 6 patients (33%).

Conclusions

The addition of valproic acid to oral etoposide in a population of advanced PROC with poor parameters was not beneficial.

Clinical trial identification

CTRI/2020/01/022781.

Editorial acknowledgement

Legal entity responsible for the study

Student Investigator: DR Nakka Thejeswar; Guide: Dr Prasanth Ganesan; Institute: JIPMER.

Funding

JIPMER- Jawaharlal Institute of Medical Education and Research.

Disclosure

All authors have declared no conflicts of interest.