Tocotrienol and Bevacizumab in Metastatic Colorectal Cancer

Inclusion criteria

• Histopathologically verified adenocarcinoma of the colon or rectum
• Metastatic disease
• Planned treatment with FOLFOX or capecitabine combined with bevacizumab
• Evaluable disease according to RECIST 1.1
• Performance status 0-2
• Expected survival ≥ 3 months
• Patient acceptance to collection of blood samples for translational research
• Age ≥ 18 years
• Contraception during and 6 months after last dose for women of childbearing potential (less than one year amenorrhea and not undergone hysterectomy, bilateral salpingectomy or bilateral oophorectomy) and for male patients with a fertile partner. Hormonal contraception, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence is accepted.
• Adequate bone marrow function, liver function, and renal function (within 7 days prior to inclusion):

• WBC ≥ 3.0 x 109/l or neutrophils (ANC) ≥ 1.5 x 10^9/l
• Platelet count ≥ 100 x 10^9/l
• Hemoglobin ≥ 6.0 mmol/l
• Serum bilirubin ≤ 2.0 x ULN
• Serum transaminase ≤ 2.5 x ULN
• Serum creatinine ≤ 1.5 ULN
• Urine dipstick for protein ≤ 2+, if the dipstick shows protein ≥ 2+, 24 hour urine testing must be performed and show protein contents ≤ 1g.
• Written and orally informed consent

Exclusion criteria

• Other active malignant disease within 5 years prior to inclusion in the study.
• Other experimental therapy within 28 days prior to treatment initiation.
• Underlying medical disease not adequately treated.
• Surgery, including open biopsy, within 4 weeks prior to first dose of bevacizumab.
• Cerebral vascular attack, transient ischemic attack or subarachnoid hemorrhage within six months before start of treatment
• Bleeding tumor
• Pregnant or breastfeeding women
• Fertile patients not willing to use effective methods of contraception during treatment and for six months after end of treatment.
• Hypersensitivity to one or more active substances or auxiliary substances