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

• Drug: Sodium Valproate
• Drug: Panitumumab
• Drug: Cetuximab

Inclusion Criteria

1. Age ≥ 18 years.
2. Histological diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of colorectalrelating to the colon or rectum in the large bowel/intestine cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs.
3. Metastatic colorectal cancer that is being treated with non-curative intent. This may be because the disease is anatomically not resectable, resectionsurgical removal of tissue or part/all of an organ is contra-indicated for any reason, or the patient refuses resection.
4. Measurable disease as assessed by CT scan (by RECIST 1.1).
5. Evidence of RAS wild type status (KRAS exons 2, 3 and 4 and NRAS exons 2, 3, and 4) as assessed by the investigators’ choice of testing laboratory.
6. ECOG performance status 0, 1.
7. Suitable, as deemed by the investigator, for maintenance treatment with panitumumab or cetuximab alone or in combination with oral sodium valproate.
8. Completed four months of first-line induction treatment with fluoropyrimidine-based chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells (which may be intravenousinto or within a vein or oral, in which case 15 weeks of treatment is required; and either alone or in combination with oxaliplatin or irinotecan) and anti-EGFR monoclonal antibody (panitumumab or cetuximab) without progressive disease.
9. Prior palliative radiotherapy is allowed, provided that (i) no concurrent chemotherapy was administered, (ii) at least 2 weeks after completion of therapy has elapsed before enrolment, and (iii) any toxicities have resolved or are Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells 1. Prior fluoropyrimidine chemotherapy given concurrent with radiation as neoadjuvant treatment for rectal cancer is allowed.
10. Adequate hepatic function with serum total bilirubin < x1.5 upper limit of normal range and ALT or AST < x3 upper limit of normal range.
11. Adequate bone marrowsoft, spongy tissue found in bones that makes blood cells function with plateletssmall disc-shaped blood cells that clump together to form clots to stop bleeding ≥ 80 X 109/L; neutrophilsa type of white blood cell that act as a first responder to infections in the body ≥ 1.5 X 109/L; haemoglobin ≥ 8g/dL.
12. Adequate renal function, with calculated creatinine clearance ≥ 50 mL/min.
13. Any abnormalities in magnesium are not > Grade 2. Any abnormalities in total calcium are not > Grade 1. Total calcium should be corrected for albumin level as per the institution’s usual calculation method. Serum potassium levels should be above 4.0 mmol/L.
14. Archival formalin-fixed paraffin embedded (FFPE) tumoura tissue mass that forms from groups of unhealthy cells tissuea group of cells that work together to perform a function is available for storage and use by the central laboratory.
15. Life expectancy of at least 12 weeks.
16. Women and partners of women of childbearing potential must agree to use adequate contraception uninterrupted for the duration of receiving VPA, cetuximab and panitumumab, and for an additional 2 months after the last dosethe amount of medication taken of cetuximab and 6 months after the last dose of panitumumab. Adequate contraceptive measures are barrier methods (condoms, diaphragm); oral, injectable, or implant birth control; or abstinence.
17. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
18. Written informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment. including consent for donation of tumour tissue for biomarker studies and collection of peripheral bloodthe red bodily fluid that transports oxygen and other nutrients around the body for research.