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

Sponsor
National Cancer Institute, Naples
Study ID
NCT06714357
Phase
PHASE2
Status
Recruiting
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Conditions

  • Colorectal Cancer Metastatic

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • irinotecan — DRUG
    Administered at the dosage of 180 mg/m2 over 60 minutes
  • panitumumab — DRUG
    Administered as 60 minutes, or 90 minutes for doses over 1000 mg, intravenous infusion at the dosage of 6 mg/kg
  • Valproic Acid (VPA) — DRUG
    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).

Study Details

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.

Key Dates

Start date
Mar 12, 2025
Status verified
Dec 2025
Primary completion
Dec 20, 2026
Completion
Jun 20, 2027

Study Design

Enrollment
130 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: STUDY PART 1 - ARM A - control arm
    Patients will continue to receive standard rechallenge with irinotecan and panitumumab until treatment failure, unacceptable toxicity, physician's decision, patient's refusal, or any other discontinuation criteria.
  • Experimental: STUDY PART 1 - ARM B - experimental arm
    Patients will continue to receive standard rechallenge with irinotecan and panitumumab in combination with VPA until treatment failure, unacceptable toxicity, physician's decision, patient's refusal, or any other discontinuation criteria.

Primary Outcome Measure

Study Part 1 - Progression Free Survival rate at 16 weeks in the two arms. [ Time Frame: up to 16 weeks from randomization ]

Central Contacts

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