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 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) 100000 /mm3, hemoglobin > 9 g/dL, absolute neutrophil count > 1500/mm3.
• Alkaline phosphatase limit ≤ 2.5 times the ULN ( 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 prote