Phase II Study of Perindopril and Regorafenib in mCRC

Inclusion Criteria: Patients with metastatic colorectal cancer (mCRC) who have progressed on/after, or are intolerant to all approved drugs for CRC and are eligible for regorafenib. In order to be eligible, all inclusion criteria must be met. A patient must: * Understand, be willing to give consent, and sign a written informed consent form (ICF) prior to undergoing any study-specific procedure * Be male or female and ≥ 18 years of age * Histological or cytological documentation of adenocarcinoma of the colon or rectum. * Patients with metastatic colorectal cancer (Stage IV) previously treated with fluoropyrimidine-based chemotherapy, oxaliplatin, irinotecan, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy. * Progression during or within 3 months following the last administration of approved standard therapies, or have experienced intolerance to previous therapy. * Metastatic CRC patients with measurable or non-measurable disease * Life expectancy of at least 3 months * Have an Eastern Cooperative Oncology Group performance status of 0 or 1 (within 14 days prior to the initiation of study treatment) * Have adequate bone marrow, liver function, and renal function as measured by the following laboratory assessments conducted within 7 days prior to the initiation of study treatment: * Total bilirubin \< 1.5 times the upper limit of normal (ULN) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 times the ULN (\< 5 times ULN for patients with liver involvement of their cancer) * Lipase \< 1.5 times the ULN * Serum creatinine \< 1.5 times the ULN * Glomerular filtration rate \> 30 mL/min/1.73 m2 according to the modified diet in renal disease abbreviated formula * International normalized ratio (INR) of prothrombin time (PT; PT-INR) and partial thromboplastin time (PTT) \< 1.5 times the ULN * Platelet count \> 100000 /mm3, hemoglobin \> 9 g/dL, absolute neutrophil count \> 1500/mm3. * Alkaline phosphatase limit ≤ 2.5 times the ULN (\< 5 times ULN for patients with liver involvement of their cancer) * If female and of childbearing potential, have a NEGATIVE result on a pregnancy test performed a maximum of 7 days before initiation of study treatment. * If female and of childbearing potential or if male, must agree to use adequate contraception (e.g., abstinence, intrauterine device, oral contraceptive, or double-barrier method) based on the judgment of the investigator or a designated associate from the date on which the ICF is signed until 6 months after the last dose of study drug. Exclusion Criteria: Patients who meet the following criteria at the time of screening will be excluded: * Patients with hypotension (less than 90/60mm Hg) or at risk of symptomatic hypotension (fainting or dizziness) will be excluded. * Prior treatment with regorafenib or any VEGFR-targeting kinase inhibitor. * Previous assignment to treatment during this study. Patients permanently withdrawn from study participation will not be allowed to re-enter the study. * Concurrent cancer requiring treatment that is distinct in primary site or histology from colorectal cancer. * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication. * Unstable/uncontrolled cardiac disease including: congestive heart failure \> New York Heart Association (NYHA) class 2; unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months); myocardial infarction less than 6 months before start of study drug; cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted). * Uncontrolled hypertension. (Systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg despite optimal medical management). * Patients with phaeochromocytoma. * Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication. * Ongoing infection \> grade 2 NCI-CTCAE version 4.03 * Known history of human immunodeficiency virus (HIV) infection. * Known history of chronic hepatitis B or C. * Patients with seizure disorder requiring medication. * Symptomatic metastatic brain or meningeal tumors unless the patient is \> 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry. Also the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies) * History of organ allograft * Patients with evidence or history of bleeding diasthesis, including patients who have had a transfusion and/or radiographic endoscopic or elective operative interaction to control the bleeding or hemorrhage event within four weeks prior to the study * Non-healing wound, ulcer, or bone fracture. * Renal impairment or failure requiring hemo-or peritoneal dialysis. * Patients with severe hepatic impairment. * Dehydration NCI-CTC version 4.03 grade \> 1. * Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results * Any illness or medical conditions that are unstable or could jeopardize the safety of the study * Interstitial lung disease with ongoing signs and symptoms at the time of informed consent. * Persistent proteinuria of Common Terminology Criteria (CTC) Grade 3 or higher. Quantification of proteinuria done by urinary protein/creatinine ratio on a random urine sample preferably taken at mid-morning. If protein/creatinine ratio is greater than 30g/mol Creat, then a 24-hour urine protein test should be performed to confirmed Grade 3 or higher proteinuria (\> 3.5 g/24 hours). * Patients unable to swallow oral medications * Any malabsorption condition * Unresolved toxicity higher than NCI-CTCAE (version 4.03) Grade 1 attributed to any prior therapy/procedure excluding alopecia and oxaliplatin induced neurotoxicity ≤Grade 2 * Patients who are hypersensitive to perindopril, as well as those hypersensitive to regorafenib, sorafenib, drugs in the same class or any ingredient in the formulation. * Patients who cannot tolerate the full dose of perindopril (4 mg) for any reason. * Patients receiving systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, hormonal therapy and experimental or approved therapies during this trial or within 14 days before starting to receive study medication. In addition, patients will be excluded for the following reasons (From perindopril monograph). * Patients with a history of hereditary/idiopathic angioedema, or angioedema related to previous treatment with an angiotensin converting enzyme inhibitor. * Pregnant women or those planning to become pregnant, nursing women. * Patients with hereditary problems of galactose intolerance, glucose-galactose malabsorption, or the Lapp lactase deficiency. * Patients with pre-existing anti-hypertension treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) are to be excluded. Co-administration of ACE inhibitors, including COVERSYL®, with other agents blocking the Renin-Angiotensin System (RAS), such as ARBs or aliskiren-containing drugs, will not be allowed, since such treatment has been associated with an increased incidence of severe hypotension, renal failure, and hyperkalemia.