Randomized phasE 2 study of Valproic acid in combination with bevacizumab and Oxaliplatin/fLUoropyrimidine regimens in patients with ras-mutated metastaTIc cOlorectal caNcer

Phase 1

Conditions: patients with ras-mutated metastaTIc colorectal cancer
MedDRA version: 20.0Level: LLTClassification code 10007446Term: Carcinoma of rectumSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-001414-15-IT

Lead Sponsor: ISTITUTO NAZIONALE TUMORI - IRCCS FONDAZIONE PASCALE

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 200

Inclusion Criteria

Main inclusion criteria
•Age = 18
•Histologically confirmed diagnosis of colorectal adenocarcinoma
•Stage IV of disease (according to TNM 8th edition)
•RAS mutations
•Clinical or radiologic evidence of disease (at least one target according to RECIST 1.1)
•ECOG performance status 0 to 1
•Life expectancy > 3 months
•Use of an acceptable mean of contraception for men and women of childbearing potential
•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
•Written informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

Main exclusion criteria
•Tumors without RAS mutations
•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)
•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)
•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)
•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
•Known dihydropyrimidine dehydrogenase (DPD) deficiency
•Pregnancy or nursing
•Concomitant pathologies or laboratory alterations or concomitant medications use that prevent or contraindicate the use of study drugs
•Brain metastases