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

Required: KRAS wild-type (exons 2, 3, and 4)

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.

Required: NRAS wild-type (exons 2, 3, and 4)

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.

Excluded: BRAF V600E

BRAFV600E mutant CRC [excluded].

Excluded: HER2 (ERBB2) IHC score of 3+

CRC with HER2 IHC score of 3+ [excluded]. Note that IHC evaluation for HER2 amplification is required for determining eligibility.

Must have received: fluoropyrimidine-based chemotherapy — first-line induction

Completed four months of first-line induction treatment with fluoropyrimidine-based chemotherapy (which may be intravenous 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.

Must have received: anti-EGFR monoclonal antibody (panitumumab, cetuximab) — first-line induction

Completed four months of first-line induction treatment with fluoropyrimidine-based chemotherapy ... and anti-EGFR monoclonal antibody (panitumumab or cetuximab) without progressive disease.

Cannot have received: chemotherapy

Exception: adjuvant chemotherapy given in association with complete resection of primary colon or rectal cancer (no relapse for at least 6 months after completion) and/or complete resection of limited colorectal metastases to liver and/or lung (no relapse for at least 6 months after completion)

Prior chemotherapy before first-line induction chemotherapy [excluded]. Exceptions are adjuvant chemotherapy which was given in association with (i) complete resection of primary colon or rectal cancer provided there is no clinical, radiological or biochemical evidence of relapse for at least 6 months after completion of adjuvant treatment, and/or (ii) complete resection of limited colorectal metastases to liver and/or lung provided there is no clinical, radiological or biochemical evidence of relapse for at least 6 months after completion of adjuvant treatment.

Cannot have received: HDAC inhibitor (vorinostat, panobinostat, belinostat, tucidinostat, chidamide, romidepsin, sodium valproate, phenylbutyrate)

Prior or current treatment with HDAC inhibitor or compounds with HDAC inhibitor-like activity, including hydroxamic acid (e.g vorinostat/zolinza, panobinostat/farydak. Belinostat/beleodaq), benzamide (tucidinostat/epidaza/chidamide), cyclic tetrapeptide (Romidepsin/Istodax) or carboxylic acid (e.g sodium valproate, phenylbutyrate) based HDAC inhibitors.