Phase 1 Trial To Evaluate mFOLFOX6 With Selinexor In Patients With Metastatic Colorectal Cancer

Inclusion Criteria: 1. Patients with histologically confirmed diagnosis of colorectal cancer presenting with unresectable stage IV (UICC) disease (primary tumor may be present) 2. Patients who are feasible for treatment with FOLFOX (prior adjuvant or palliative treatment is allowed) 3. ECOG (Eastern Cooperative Oncology Group) Performance status ≤ 1 4. Life expectancy \> 3 months 5. Age ≥18 years 6. Haematologic function as follows (5% deviation allowed): * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L * platelets ≥ 100 x109/L * hemoglobin ≥ 9 g/dl or 5.59 mmol/l 7. Adequate liver function as follows (10% deviation allowed) * serum alanine transaminase (ALT) ≤ 2.5 x ULN (in case of liver metastases \< 5 x ULN) * total bilirubin ≤ 1.5 x ULN (patients with Gilbert's syndrome total bilirubin ≤2.5 x ULN) 8. Adequate renal function as follows (10% deviation allowed) · creatinine ≤ 1.5 x ULN 9. Signed written informed consent 10. Women of child-bearing potential must have a negative pregnancy test Exclusion Criteria: adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy; 2. Treatment with any systemic anticancer therapy ≤ 3 weeks prior to cycle 1 day 1 3. Uncontrolled active infection (Hepatitis B and C infection are NOT exclusion criteria) and/or known HIV infection; 4. Renal failure requiring haemodialysis or peritoneal dialysis; 5. Patients who are pregnant or breast-feeding; 6. Patients with significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea resulting in inability to swallow oral medications; 7. Presence of symptomatic Central nervous system (CNS) metastasis 8. Unresolved toxicity from previous anti-cancer therapy or incomplete recovery from surgery, in particular oxaliplatin-induced peripheral neuropathy \> grade 1. 9\. Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic event.