Valproic acid; Sodium valproate for Metastatic colorectal cancer (RAS-mutated)

Inclusion criteria

• {"criterion_text":"- Age = 18"}
• {"criterion_text":"- Histologically confirmed diagnosis of colorectal adenocarcinoma"}
• {"criterion_text":"- Stage IV of disease (according to TNM 8th edition)"}
• {"criterion_text":"- RAS mutations"}
• {"criterion_text":"- Clinical or radiologic evidence of disease (at least one target according to RECIST 1.1)"}
• {"criterion_text":"- ECOG performance status 0 to 1"}
• {"criterion_text":"- Life expectancy > 3 months"}
• {"criterion_text":"- Use of an acceptable mean of contraception for men and women of childbearing potential"}
• {"criterion_text":"- Adequate recovery from previous surgery. At least 28 days should elapse from a surgical procedure or from performing a biopsy for the enrolment into the study"}
• {"criterion_text":"- Written informed consent"}

Exclusion criteria

• {"criterion_text":"- Tumors without RAS mutations"}
• {"criterion_text":"- Prior chemotherapy or any other medical treatment for advanced mCRC (previous adjuvant chemotherapy is allowed if ended > 6 months before relapse or > 24 months if the adjuvant treatment included oxaliplatin)"}
• {"criterion_text":"- Radiotherapy to any site for any reason within 28 days prior to randomization (palliative radiotherapy to bone lesions is allowed if = 14 days before randomization)"}
• {"criterion_text":"- Any other invasive malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer or surgically resected prostate cancer with normal PSA)"}
• {"criterion_text":"- Patient who have had prior treatment with an HDAC inhibitor and patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid"}
• {"criterion_text":"- Known dihydropyrimidine dehydrogenase (DPD) deficiency"}
• {"criterion_text":"- Pregnancy or nursing"}
• {"criterion_text":"- Concomitant pathologies or laboratory alterations or concomitant medications use that prevent or contraindicate the use of study drugs"}
• {"criterion_text":"- Brain metastases"}

Primary endpoints

• {"endpoint_text":"- PFS progression-free survival","definition_or_measurement_approach":"Investigator-assessed progression-free survival (PFS) as the primary endpoint (PFS assessed by investigators, investigator-assessed, IA)."}

Secondary endpoints

• {"endpoint_text":"- centrally reviewed PFS (CR-PFS)","definition_or_measurement_approach":"Centrally reviewed progression-free survival (CR-PFS) assessed by independent central review."}

Other endpoints

• {"endpoint_text":"- overall survival (OS)","definition_or_measurement_approach":"Overall survival (OS) measured from randomization to death from any cause."}
• {"endpoint_text":"- quality of life (EORTC QLQ C30 + CR 29)","definition_or_measurement_approach":"Patient-reported quality of life using EORTC QLQ-C30 and CR29 questionnaires."}
• {"endpoint_text":"- objective response rate (RECIST1.1)","definition_or_measurement_approach":"Objective response rate assessed by RECIST v1.1 criteria."}
• {"endpoint_text":"- adverse events (CTCAE 4.03 version)","definition_or_measurement_approach":"Safety assessed by recording adverse events graded by CTCAE v4.03 (as stated)."}
• {"endpoint_text":"- metastases resection rate (R0/R1/R2)","definition_or_measurement_approach":"Rate of metastases resections with classification of residual disease (R0/R1/R2)."}
• {"endpoint_text":"- To evaluate mechanistically –based pharmacokinetic/pharmacodynamic biomarkers on blood samples","definition_or_measurement_approach":"Mechanistic PK/PD biomarker analyses on blood samples."}
• {"endpoint_text":"- To explore prognostic factors and predictive biomarkers on blood samples, primary tumors, and on resected metastases","definition_or_measurement_approach":"Exploratory analyses of prognostic and predictive biomarkers on blood, primary tumour tissue and resected metastases."}

Italy

Earliest CTIS Part Ii Submission Date

29-10-2024

Latest Decision Or Authorization Date

22-07-2025

Processing Time Days

266

Number Of Sites

8

Number Of Participants

200

Primary sponsor

Full Name

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy