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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
90
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.
Panitumumab 6 mg/kg IV every 2 weeks or cetuximab 500 mg/m2 IV every 2 weeks; Refer to arm description.
Panitumumab 6 mg/kg IV every 2 weeks or cetuximab 500 mg/m2 IV every 2 weeks; Refer to arm description.
Royal North Shore Hospital
Saint Leonards, New South Wales, Australia
RECRUITINGWestern Sydney Local Health District
Westmead, New South Wales, Australia
RECRUITINGProgression free survival
Progression free survival (PFS) will be defined as the interval from date of registration or randomisation to the date of first evidence of disease progression (measured by RECIST v1.1 criteria) or death whichever occurs first, in each treatment arm.
Time frame: 12 Months from randomisation
Overall Survival
Overall survival (OS) will be defined as the interval from date of registration or randomisation to date of death from any cause.
Time frame: 12 Months from randomisation
Objective response rates (ORRs)
ORRs will be calculated as the proportion of participants in each arm who are assessed as having a complete or partial response measured by RECIST v1.1.
Time frame: 12 Months from randomisation
Quantification of the incidence of treatment-emergent adverse events according to CTCAE V5.0
Safety of each treatment arm will be assessed by evaluating the number and severity (grade) of adverse events reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0).
Time frame: 12 Months from randomisation
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia
RECRUITINGQueen Elizabeth Hospital
Adelaide, South Australia, Australia
RECRUITINGSouthern Adelaide Local Health Network Incorporated
Bedford Park, South Australia, Australia
RECRUITINGGrampians Health
Ballarat Central, Victoria, Australia
RECRUITINGEastern Health
Box Hill, Victoria, Australia
RECRUITINGPeninsula Health
Frankston, Victoria, Australia
RECRUITINGPeter MacCallum Cancer Institute
Melbourne, Victoria, Australia
RECRUITINGAustin Health
Melbourne, Victoria, Australia
RECRUITING...and 1 more locations