regorafenib in subjects with antiangiogenic-naive and chemotherapy-refractory advanced colorectal cancer

Conditions: Colorectal Neoplasms

Summary: to determine the efficacy (as measured by progression-free survival \[pfs\] rate at 8 weeks) of regorafenib in subjects with metastatic colorectal cancer (crc) whose disease is refractory to standard therapies and who were never exposed to antiangiogenic therapy.


Eligibility criteria:
inclusion criteria: * male or female subjects ≥18 years of age; * histological or cytological confirmation of adenocarcinoma of the colon or/and rectum; * subjects with metastatic colorectal cancer (crc) whose disease progressed or who were intolerant to standard chemotherapy based on fluoropyrimidine, oxaliplatin, irinotecan, and an anti-egfr therapy if ras wild-type. this progression must be during or within 4 months following the last administration of standard therapies. * measurable disease according to response evaluation criteria in solid tumors (recist) criteria, version 1.1. * eastern cooperative oncology group (ecog) performance status of 0 or 1 * adequate bone-marrow, liver, and renal function * women of childbearing potential and men must agree to use adequate contraception when sexually active during the study and for at least 8 weeks after the last study drug administration. exclusion criteria: * prior treatment with an antiangiogenic agent; * congestive heart failure of new york heart association (nyha) class 2 or worse; * 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 \>140 mmhg or diastolic pressure \>90 mmhg despite optimal medical management); * ongoing acute or chronic infection (\> grade 2 nci-ctcae v 4.03); * arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism (except for adequately treated catheter-related venous thrombosis occurring more than one month before the start of study medication) events within 6 months of study enrollment. subjects being treated with low-weight heparin are allowed to participate as long as dose is limited to prophylactic use. * any history of or currently known brain metastases (head ct/mri will be performed during screening period if brain metastases are suspected) * previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years before study entry, except for curatively treated cervical cancer in situ, in situ ductal breast cancer, non-melanoma skin cancer and superficial bladder tumors; * last chemotherapy dose or any other anti-cancer therapy administered in less than 4 weeks from start of study treatment; * use of therapeutic anticoagulation; * proteinuria \> 3.5 g/24 hours measured by urine protein-creatinine ratio from a random urine sample (grade 3, nci-ctcae v 4.03) on urinalysis screening result. if there is medical history of proteinuria, previous urinalysis results should be considered and/or performed so at least 2 results separated by at least 2 weeks are available; * history of interstitial lung disease with ongoing signs and symptoms at the time of informed consent; * non-healing wound, non-healing ulcer, or non-healing bone fracture; * subjects with evidence or history of any bleeding diathesis, irrespective of severity; * any hemorrhage or bleeding event ≥ grade 3 nci-ctcae v 4.03 within 4 weeks prior to the start of study medication; * known history of human immunodeficiency virus (hiv) infection; * history of active hepatitis b or c, or chronic hepatitis b or c requiring treatment with antiviral therapy; * pregnancy or breastfeeding.

Keywords: colorectal cancer regorafenib