Clinical trial NCT02465502 (phase 2, status: completed)
Conditions: colorectal neoplasms
ICD codes: C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2
Drugs: regorafenib (stivarga, bay73-4506)
SMILES: O=[Zn]
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.