NCT05694936

Combining Sodium Valproate With Standard-of-care EGFR (Epidermal Growth Factor Receptor) Monoclonal Antibody Treatment in Patients With Metastatic Colorectal Cancer

A Phase II Trial to Determine the Efficacy of Combining the HDAC Inhibitor Sodium Valproate With EGFR Monoclonal Antibody (Panitumumab or Cetuximab) Maintenance in the First-line Treatment of Patients With RAS Wild Type Metastatic Colorectal Cancer (VADER Study).

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Sponsor: Australasian Gastro-Intestinal Trials Group · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The aim of this study is to determine the efficacy of combining the histone deacetylase (HDAC) inhibitor sodium valproate (VPA) with anti-EGFR monoclonal antibody (panitumumab or cetuximab) maintenance in the first-line treatment of patients with RAS wild type metastatic CRC.

Detailed description

The primary objective is to evaluate progression free survival (PFS) in patients with RAS wild type metastatic CRC treated in the first-line with VPA plus panitumumab or cetuximab maintenance, or panitumumab or cetuximab maintenance alone. The secondary objectives are (i) to evaluate overall survival (OS) and objective response rates (ORRs; RECIST v 1.1) in patients with RAS wild type metastatic CRC treated in the first-line with VPA plus panitumumab or cetuximab maintenance, and panitumumab or cetuximab maintenance alone; and (ii) to evaluate the safety (NCI CTCAE v5.0) of first-line maintenance treatment with VPA plus panitumumab or cetuximab, and panitumumab or cetuximab maintenance alone in patients with RAS wild type metastatic CRC. The tertiary and exploratory objectives are: * To evaluate Health-Related Quality of Life (EORTC QLQ-C30 and EQ-5D-5L) in patients with RAS wild type metastatic CRC treated in the first-line with VPA plus panitumumab or cetuximab maintenance, and panitumumab or cetuximab maintenance alone. * Exploratory analyses including, but not limited to: (i) Determining whether changes in levels of histone acetylation in peripheral blood mononuclear cells (PBMCs) are associated with improved efficacy with VPA plus anti-EGFR monoclonal antibody maintenance treatment; and (ii) determining whether potential resistance-conferring mutations in circulating tumour DNA (ctDNA) are associated with efficacy outcomes in patients treated with anti-EGFR monoclonal antibody maintenance.

Conditions

• Metastatic Colorectal Cancer

Interventions

Type	Name	Description
DRUG	Sodium Valproate	Sodium valproate oral continuously in a twice daily dose (Initial dose of 600mg/d up-titrated to target daily dose of 20 mg/kg/d at Cycle 1 Day 13, then dose adjusted to maintain serum VPA levels within the target range of 50-100 μg/mL); Refer to arm description.
DRUG	Panitumumab	Panitumumab 6 mg/kg IV every 2 weeks or cetuximab 500 mg/m2 IV every 2 weeks; Refer to arm description.
DRUG	Cetuximab	Panitumumab 6 mg/kg IV every 2 weeks or cetuximab 500 mg/m2 IV every 2 weeks; Refer to arm description.

Timeline

• Start date: 2023-01-23
• Primary completion: 2026-04-30
• Completion: 2027-06-01
• First posted: 2023-01-23
• Last updated: 2025-09-18

Locations

11 sites across 1 country: Australia