Clinical trial NCT02835924 (phase 2, status: completed)
Conditions: metastatic colorectal cancer
ICD codes: C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2
Drugs: regorafenib
SMILES: [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
Eligibility criteria:

        Inclusion Criteria:

          1. Signed informed consent (IC) obtained before any study specific procedures. Subjects
             must be able to understand and willing to sign a written informed consent.

          2. Male or female subjects 18 years of age.

          3. Life expectancy of at least 3 months.

          4. Histological or cytological documentation of adenocarcinoma of the colon or rectum.
             All other histological types are excluded.

          5. Measurable metastatic stage IV disease with at least 1 measurable metastatic lesion
             following RECIST criteria v 1.1.

          6. Subjects with metastatic colorectal cancer (Stage IV).

          7. Progression during or within 3 months following the last administration of approved
             standard therapies which must include fluoropyrimidine, oxaliplatin, irinotecan, an
             anti-VEGF and an anti-EGFR (if RAS WT)

          8. Subjects treated with oxaliplatin in an adjuvant setting should have progressed during
             or within 6 months of completion of adjuvant therapy

          9. Subjects who progress more than 6 months after completion of oxaliplatin containing
             adjuvant treatment must be retreated with oxaliplatin-based therapy to be eligible.
             Subjects who have withdrawn from standard treatment due to unacceptable toxicity
             warranting discontinuation of treatment and precluding retreatment with the same agent
             prior to progression of disease will also be allowed into the study

         10. ECOG Performance Status of 0 or 1(within 14 days prior to the initiation of study
             treatment)

         11. Adequate bone marrow, liver and renal function as assessed by the following laboratory
             requirements:

               -  Total bilirubin =1.5 x the upper limit of normal (ULN).

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 x ULN
                  (5 x ULN for subjects with liver involvement of their cancer).

               -  Alkaline phosphatase limit = 2.5 x ULN (5 x ULN for subjects with liver and/or
                  bone involvement of their cancer).

               -  Lipase = 1.5 x the ULN.

               -  Serum creatinine 1.5 x the ULN or = 30 mL/min as calculated using the
                  Cockcroft-Gault equation.

               -  Platelet count >100000/mm3, hemoglobin >9 g/dL, absolute neutrophil count (ANC)
                  >1500/mm3.

               -  International normalized ratio (INR)/ Partial thromboplastin time (PTT) 1.5 x
                  ULN. (Subjects who are therapeutically treated with an agent such as warfarin or
                  heparin will be allowed to participate provided that no prior evidence of
                  underlying abnormality in coagulation parameters exists. Close monitoring of at
                  least weekly evaluations will be performed until INR/PTT is stable based on a
                  measurement that is pre-dose as defined by the local standard.

               -  Blood transfusion to meet the inclusion criteria will not be allowed.

         12. Women of childbearing potential and men must agree to use adequate contraception
             before entering the program until at least 8 weeks after the last study drug
             administration. The investigator or a designated associate is requested to advise the
             subject on how to achieve an adequate birth control. Adequate contraception is defined
             in the study as any medically recommended method (or combination of methods) as per
             standard of care. Women of childbearing potential must have a blood or urine pregnancy
             test performed a maximum of 7 days before start of study treatment, and a negative
             result must be documented before start of study treatment.

        Exclusion Criteria:

          1. Prior treatment with regorafenib.

          2. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             before start of study drug

          3. Pregnant or breast-feeding subjects:

          4. Congestive heart failure = New York Heart Association (NYHA) class 2.

          5. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3
             months).

          6. Myocardial infarction less than 6 months before start of study drug.

          7. Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are
             permitted).

          8. Uncontrolled hypertension. (Systolic blood pressure > 140 mmHg or diastolic pressure
             >90 mmHg despite optimal medical management).

          9. Arterial or venous thromboembolism within 6 months prior to randomization.

         10. Pleural effusion or ascites that causes respiratory compromise (CTCAE Grade 2
             dyspnea).

         11. Ongoing infection > Grade 2 CTCAE v. 4.0.

         12. Known history of human immunodeficiency virus (HIV) infection.

         13. Known history of active hepatitis B or C, or chronic hepatitis B or C requiring
             treatment with antiviral therapy.

         14. Subjects with seizure disorder requiring medication.

         15. History of organ allograft.

         16. Subjects with evidence or history of any bleeding diathesis, irrespective of severity.

         17. Any hemorrhage or bleeding event = CTCAE Grade 3 within 4 weeks prior to the start of
             study medication.

         18. Non-healing wound, ulcer, or bone fracture.

         19. Renal failure requiring hemo-or peritoneal dialysis.

         20. Dehydration CTCAE v. 4.0 Grade = 1.

         21. Substance abuse, medical, psychological or social conditions that may interfere with
             the subject's participation in the study or evaluation of the study results.

         22. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in
             the formulation.

         23. Any illness or medical conditions that are unstable or could jeopardize the safety of
             the subject and his/her compliance in the study.

         24. Interstitial lung disease with ongoing signs and symptoms

         25. Persistent proteinuria of CTCAE Grade 3 (>3.5g/24 hours).

         26. Subjects unable to swallow oral medications.

         27. Any malabsorption condition.

         28. Unresolved toxicity higher than CTCAE (v. 4.0) > Grade 1 attributed to any prior
             therapy/procedure excluding alopecia, hypothyroidism and oxaliplatin induced
             neurotoxicity > Grade 2.

         29. Subjects treated with strong CYP3A4 inhibitors or inducers (refer to appendix 8 and to
             section 6.3.8. Prohibited concomitant medication).

         30. Subjects receiving G-CSF within 3 weeks prior to signing the ICF

         31. Concomitant participation or participation within the last 30 days in another clinical
             trial

         32. Systemic anticancer therapy including cytotoxic therapy, signal transduction
             inhibitors, immunotherapy, and hormonal therapy during this trial or within 4 weeks
             (or within 6 weeks for mitomycin C) before starting to receive study medication.