Clinical trial NCT02175654 (phase 2, status: terminated)
Conditions: colorectal neoplasms, metastatic disease
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
Reason stopped: 
    the trial was prematurely closed due to lack of accrual
  
Eligibility criteria:

        Inclusion Criteria:

          1. Signing of the informed consent form.

          2. The patient must be able to understand the information and state expressly his or her
             desire to take part in the study.

          3. Age ≥ 18 years.

          4. Histologically or cytologically documented adenocarcinoma of the colon or rectum.

          5. Patients with metastatic colorectal cancer (stage IV) with any RAS or BRAF mutation.

          6. To have received first_line treatment with bevacizumab in combination with
             chemotherapy with the three drugs 5FU/leucovorin (LV), irinotecan and oxaliplatin
             (FOLFOXIRI), and

               -  have had radiological progression of the disease during the first_line treatment,
                  or

               -  have had radiological progression of the disease within a period of ≤ 6 months
                  after the last dose of first-line treatment, or

               -  have discontinued part or all of the first_line treatment due to toxicity and
                  have had radiological progression of the disease within a period of ≤ 6 months
                  after the last dose of first-line treatment.

             The patient will have to have received at least one cycle of bevacizumab in
             combination with FOLFOXIRI + bevacizumab as part of the first_line treatment.

             Patients may have received fluoropyrimidine_based adjuvant treatment with or without
             oxaliplatin.

          7. Existence of at least one measurable unidimensional lesion using CT or MRI based on
             the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1

          8. Overall Eastern Cooperative Oncology Group (ECOG) performance ≤1.

          9. Patient's commitment to compliance with the oral medication throughout the duration of
             the study

         10. Life expectancy of at least 3 months

         11. Adequate bone marrow, renal and hepatic function, defined as:

               -  Neutrophils ≥ 1500/mm3

               -  Platelets ≥100,000/mm3

               -  Haemoglobin ≥ 9,0 g/dL

               -  Serum Creatinine ≤ 1.5 x LSN

               -  Bilirubin levels ≤ 1.5 x LSN

               -  AST and ALT levels ≤ 2.5 x ULN (if liver metastases < 5 x ULN)

        Exclusion Criteria:

          1. Prior treatment with regorafenib.

          2. Assignment prior to treatment during this study. Patients who are permanently
             withdrawn from participation in the study treatment will not be allowed to return to
             it.

          3. Prior or concurrent presence of another neoplastic disease that is different in terms
             of tumour site and histology of the colorectal cancer in the 5 years prior to the
             inclusion of the patient in the study, except in situ cervical cancer, superficial
             bladder carcinoma [Ta (non-invasive), Tis (carcinoma in situ) and T1 (tumour invades
             lamina propria)] and non-melanoma skin tumours.

          4. Presence or history of brain metastases or meningeal tumours.

          5. Major surgery, open biopsy or traumatic injury within 28 days prior to the start of
             patient treatment with the study medication.

          6. Extended-field radiotherapy within 4 weeks prior to inclusion or limited-field
             radiotherapy in the previous 2 weeks. Patients must have recovered from all
             treatment-related toxicities.

          7. Pregnant or breastfeeding women. Women of childbearing age must use adequate
             contraception. Women of childbearing age must have a negative pregnancy test within 7
             days prior to starting with the study medication.

          8. Women of childbearing age and men who wish to take part in the study must agree to use
             adequate contraception from the signing of the informed consent until at least 3
             months after stopping the study medication. The investigator or the person designated
             by him or her will ensure and advise as to the contraceptive methods that should be
             used.

             Appropriate contraceptive methods include abstinence, oral contraceptives, transdermal
             patches and injections of sustained-release progestin (starting at least 4 weeks
             before administration of the IMP), double-barrier method: condom or female condom
             (diaphragm or cervical/vaginal condom) plus spermicide, intrauterine device (IUD),
             intrauterine system, implant or vaginal ring (in place at least 4 weeks before
             administration of the IMP) or male partner sterilisation (vasectomy with documentation
             of azoospermia) prior to inclusion of the woman in the trial if he is the woman's only
             sexual partner.

          9. Active congestive heart failure class 2 or higher on the New York Heart Association
             (NYHA) scale.

         10. Unstable angina (angina symptoms at rest), new_onset angina (having appeared in the
             past 3 months) or acute myocardial infarction that has occurred in the 6 months prior
             to starting with the study medication.

         11. Cardiac arrhythmias that require anti-arrhythmic therapy (only beta blockers and
             digoxin would be allowed as concomitant medication for these patients).

         12. Uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic blood
             pressure > 90 mmHg) despite proper medical management.

         13. Patients with phaeochromocytoma.

         14. Pleural effusion or ascites that cause breathing difficulties (dyspnoea of grade ≥ 2
             of the CTC).

         15. Venous or arterial thromboembolism or embolic events such as cerebrovascular accidents
             (including transient ischaemic attacks), deep vein thrombosis or pulmonary
             thromboembolism that have occurred in the 6 months prior to starting with the study
             medication.

         16. Active infection > grade 2 based on the NCI CTC, v. 4.0.

         17. Human immunodeficiency virus (HIV) infection.

         18. Active hepatitis B or C, or hepatitis B or C infection that requires treatment with
             antiviral drugs.

         19. Patients with mental disorders that require medication.

         20. History of organ transplants.

         21. Patients with evidence or history of bleeding diathesis. Any bleeding or bleeding
             event > Common Toxicity Criteria for Adverse Effects (CTCAE) grade 3 in the 4 weeks
             prior to starting with the study medication.

         22. Presence of unhealed wounds, ulcers or bone fractures.

         23. Kidney failure requiring haemodialysis or peritoneal dialysis.

         24. Dehydration based on NCI CTC criteria, version 4, of > 1.

         25. Substance abuse or a history of medical, social or psychological conditions that may
             interfere with study participation or compliance with the efficacy and safety
             assessments planned in the study.

         26. Known hypersensitivity to regorafenib or any of its excipients.

         27. Presence of any disease or medical condition that might interfere with patient safety
             or may compromise treatment compliance with it.

         28. Interstitial lung disease with signs and symptoms present at the time of signing the
             informed consent.

         29. Patients who are unable to swallow oral medication.

         30. Persistent proteinuria > grade 3 based on the NCI CTC, version 4.0 (> 3.5 g/24 hours).

         31. Intestinal malabsorption syndrome.

         32. Close personal relationship with the research staff, such as family members of the
             investigator or dependents (e.g. employees or students of the research centre).

         33. Unresolved toxicity grade > 1 based on the NCI CTC, version 4.0 (except alopecia),
             related to any previous therapy or procedure.