RecruitingPhase 2NCT06714357

ValproIc Acid to Potentiate Anti-EGFR Treatment Efficacy and Prevent/Revert Resistance in Colorectal Cancer

Randomized Phase 2 Study of Valproic Acid Combined With Rechallenge Anti-EGFR Based Regimen Regimens in Pretreated Patients With RAS/BRAF Wild-type Metastatic Colorectal Cancer - VICTORIA Trial

Sponsor

National Cancer Institute, Naples

Enrollment

130 participants

Start Date

Mar 12, 2025

Study Type

INTERVENTIONAL

Conditions

Colorectal Cancer Metastatic

Summary

The investigators hypothesize that the epigenetic agent valproic acid improve the activity of anti-EGFR agents, prevent and revert the emergence of EGFR resistance, in a rechallenge setting. Correlative mechanistic studies on tissue and blood samples, liquid biopsies, could identify potential biomarkers of efficacy and help understanding the evolutionary dynamics of tumors in response to therapy thus optimizing the treatment approach with a personalized anti- EGFR treatment strategy.

Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study is testing whether adding valproic acid (a medication commonly used for epilepsy and mood disorders) to standard chemotherapy can help colorectal cancer respond better to a type of targeted therapy called anti-EGFR treatment, and prevent the cancer from becoming resistant to it. **You may be eligible if...** - You are 18 or older with confirmed metastatic (spread) colorectal cancer - Your tumor has a specific genetic profile (RAS/BRAF wild-type) confirmed by both tissue and blood tests - You previously responded well to anti-EGFR therapy and are now eligible for a rechallenge treatment with panitumumab and irinotecan - You have received at least 2 prior lines of treatment - You are in good general health (ECOG performance status 0–1) - You have adequate blood, liver, and kidney function **You may NOT be eligible if...** - You have had another cancer in the past 5 years - You have brain metastases - You have previously taken an HDAC inhibitor or valproic acid - You are pregnant or breastfeeding - You have a long QT heart rhythm condition - You have previously had an anti-EGFR rechallenge Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGirinotecan

Administered at the dosage of 180 mg/m2 over 60 minutes

DRUGpanitumumab

Administered as 60 minutes, or 90 minutes for doses over 1000 mg, intravenous infusion at the dosage of 6 mg/kg

DRUGValproic Acid (VPA)

VPA will be administered in each patient with a titration strategy to improve the compliance for the treatment, looking for a target serum level between 50 and 100 μg/mL that represents the recommended values for the treatment of epilepsy and also a useful concentration to produce the desired synergistic effect with chemotherapy based on preclinical studies. Administrated at the dosage of 500 mg/three times a day (after 7 days of gradual dose escalation).