Phase 1 Trial To Evaluate mFOLFOX6 With Selinexor In Patients With Metastatic Colorectal Cancer
Condition: Colorectal Neoplasm
MeSH terms: Colorectal Neoplasms
Intervention: Selinexor; Oxaliplatin; 5-FU; Folinic Acid
Intervention description: Dose Level 1: 40 mg on day 1, 3 and 8 in a two-weeks cycle. Dose Level 2: 60 mg on day 1, 3 and 8 in a two-weeks cycle. Dose Level 3: 80 mg on day 1, 3 and 8 in a two-weeks cycle. Dose Level -1: 20 mg on day 1, 3 and 8 in a two-weeks cycle.; 85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle; 400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3; 400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle
Intervention MeSH terms: Leucovorin; Folic Acid; Fluorouracil; Oxaliplatin; Levoleucovorin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Intervention model description: Dose level 1: Oxaliplatin at a dose of 85 mg/m2 IV over two hours (Day 1) 5-FU 400 mg/m2 IV bolus (Day 1) Leucovorin 400 mg/m2 IV over two hours (Day 1) 5-FU 2400 mg/m2 IV over 46 hours (Day 1-3) Selinexor 40 mg, PO (Day 1, 3 and 8) Dose level 2: Oxaliplatin at a dose of 85 mg/m2 IV over two hours (Day 1) 5-FU 400 mg/m2 IV bolus (Day 1) Leucovorin 400 mg/m2 IV over two hours (Day 1) 5-FU 2400 mg/m2 iv over 46 hours (Day 1-3) Selinexor 60 mg, PO (Day 1, 3 and 8) Dose level 3: Oxaliplatin at a dose of 85 mg/m2 iv over two hours (Day 1) 5-FU 400 mg/m2 iv bolus (Day 1) Leucovorin 400 mg/m2 iv over two hours (Day 1) 5-FU 2400 mg/m2 iv over 46 hours (Day 1-3) Selinexor 80 mg, PO (Day 1, 3 and 8) Dose level -1: Oxaliplatin at a dose of 85 mg/m2 IV over two hours (Day 1) 5-FU 400 mg/m2 IV bolus (Day 1) Leucovorin 400 mg/m2 IV over two hours (Day 1) 5-FU 2400 mg/m2 IV over 46 hours (Day 1-3) Selinexor 20 mg, PO (Day 1, 3 and 8)
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: metastatic

Summary:

      This trial will evaluate the combination treatment of established chemotherapy regimen
      mFOLFOX6 with Selinexor, an oral Selective Inhibitor Of Nuclear Export, in patients with
      metastatic Colorectal Cancer. The purpose is to determine the maximum tolerated dose (MTD) of
      selinexor in combination with mFOLFOX6.
    

Eligibility criteria:

        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.