What is valproic acid studying for metastatic colorectal cancer?

Valproic acid is being studied to see if it can improve anti-EGFR treatment effectiveness and help prevent or reverse resistance in patients with metastatic colorectal cancer. The study also aims to identify biomarkers that may predict how tumors respond to treatment. This research is sponsored by the National Cancer Institute, Naples.

Who may be eligible for this colorectal cancer clinical trial?

Adults aged 18 or older with metastatic colorectal adenocarcinoma that is RAS/BRAF wild-type may be eligible. Participants should have had at least two prior treatments including anti-EGFR therapy with a good response or stable disease. Both men and women can join if they meet health and laboratory requirements. Please review eligibility criteria for more details.

Is there any cost to participate in this colorectal cancer clinical trial?

Study-related care, including the study drugs and all trial visits, is provided at no cost. However, personal travel expenses or other non-study costs may not be covered and can vary. Participants should plan accordingly for any travel or accommodation needs.

Actively Recruiting

Phase 2

Age: 18Years +

All Genders

ID06714357

Phase 2 Study of Valproic Acid Added to Rechallenge Anti-EGFR Treatment with Irinotecan and Panitumumab for Patients with RASBRAF Wild-type Metastatic Colorectal Cancer

Led by National Cancer Institute, Naples · Updated on 2025-12-17

130

Participants Needed

Research Sites

26 weeks

Total Duration

AI-Summary

What this Trial Is About

Researchers are evaluating whether valproic acid can improve the effectiveness of anti-EGFR treatments and help prevent or reverse resistance in patients with advanced or metastatic colorectal cancer who have RASBRAF wild-type tumors. This randomized phase 2 study includes patients eligible for a rechallenge treatment setting, aiming to better understand tumor responses and identify biomarkers through tissue and blood sample analysis. Participants will be randomly assigned to receive either standard treatment with irinotecan and panitumumab or the same treatment combined with valproic acid VPA. Irinotecan and panitumumab are given every two weeks, while VPA is taken orally daily with dose adjustments to reach target blood levels. The study includes a safety phase for the VPA combination, and treatment continues until disease progression, unacceptable side effects, or other reasons for stopping. Throughout the study, patients will undergo tumor assessments by CT or MRI scans every 8 weeks, blood tests, and quality of life questionnaires. Toxicities will be monitored during treatment and up to 4 weeks after. Blood and tissue samples will be collected to study biomarkers related to treatment response and side effects. Follow-up will continue until death, recording subsequent treatments, with the primary outcome measuring progression-free survival at 16 weeks.

CONDITIONS

Brief Title

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

Who Can Participate

Age: 18Years +

All Genders

Eligibility Criteria

You may qualify if you...

Signed informed consent for study procedures and correlative studies
Age 18 years or older
Histologically confirmed colorectal adenocarcinoma
Diagnosis of metastatic disease
RAS/BRAF wild-type status at initial diagnosis and confirmed by liquid biopsy at study entry
Candidate for anti-EGFR rechallenge therapy with panitumumab and irinotecan
Prior major response or stable disease for 6 months or more to anti-EGFR therapy
Received at least 2 prior lines of treatment
ECOG performance status of 0 or 1
Imaging-documented measurable disease according to RECIST 1.1
Estimated life expectancy over 12 weeks
Adequate bone marrow, liver, and kidney function
Electrolytes within normal laboratory range

You will not qualify if you...

Prior malignancy within 5 years except certain skin cancers or in situ cervical cancer
Contraindications to panitumumab or irinotecan
No prior immunotherapy if dMMR or MSI-H
Prior treatment with HDAC inhibitors or valproic acid
Major surgery within 4 weeks before enrollment
Pregnancy or breastfeeding
Brain metastases
Long QT syndrome or medications prolonging QTc interval
Severe or uncontrolled systemic disease or conditions affecting study compliance
Poor cooperation or inability to understand informed consent
Participation in other interventional studies within 30 days prior to treatment
Unwillingness to use contraception if sexually active and of childbearing potential
History of interstitial pneumonitis, pulmonary fibrosis, corneal perforation, or keratitis
Hypersensitivity to valproic acid or excipients
Acute or chronic hepatitis
Severe liver disease or hepatic porphyria
Known coagulation disorders or certain genetic mutations related to mitochondria or urea cycle disorders

Research Team

Antonio Avallone, MD

Alfredo Budillon, MD

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Phase 2 Study of Valproic Acid Added to Rechallenge Anti-EGFR Treatment with Irinotecan and Panitumumab for Patients with RASBRAF Wild-type Metastatic Colorectal Cancer

On this page

AI-Summary

What this Trial Is About

Brief Title

Who Can Participate

Eligibility Criteria

Research Team

Not the Right Trial for You?

On this page

Who Can Participate

Eligibility Criteria