Regorafenib + Panitumumab for Colorectal Cancers

Exclusion Criteria

• •Any known mutation in KRAS or NRAS codons 12, 13, 59, 61, 117 or 146.
• •Prior use of regorafenib.
• •Known or suspected grade 3 allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of the trial.
• •Uncontrolled hypertension (systolic pressure greater than140 mm Hg or diastolic pressure greater than 90 mm Hg \[NCI-CTCAE v4.0\] on mean of 3 consecutive readings despite optimal medical management. Hypertension may be corrected by adding or adjusting anti-hypertensives prior to the initiation of treatment at the discretion of the practitioner.
• •Active or clinically significant cardiac disease including congestive heart failure, uncontrolled cardiac arrhythmias, or unstable angina.
• •Evidence or history of congenital or acquired hypocoagulability disorders.
• •Any hemorrhage or bleeding event greater than or equal to NCI CTCAE v.4.0 Grade 3 within 4 weeks prior to start of study medication.
• •Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism that have initiated within 6 months of start of study treatment. Stable, persistent events under appropriate management diagnosed greater than 6 months prior to treatment are allowed at the discretion of the investigator.
• •Subjects who are receiving treatment for a concurrent cancer that is distinct in primary site or histology from colorectal carcinoma, except any cancer in-situ, treated basal cell or squamous cell carcinoma, or superficial bladder tumor. Subjects surviving a cancer that was curatively treated and without evidence of disease more than 1 year before randomization are allowed. All cancer treatments must be completed at least 1 year prior to start of study treatment.
• •Patients with severe hepatic impairment (Child-Pugh Class C).
• •Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy. Baseline testing is not required.
• •Patients requiring IV antiviral or IV antibiotic treatment for ongoing infections.
• •Symptomatic metastatic brain or meningeal tumors. Baseline brain imaging is not required.
• •Presence of a non-healing wound or bone fracture.
• •Patient's with a history of kidney disease or persistent proteinuria must have less than Grade 3 proteinuria per NCI CTCAE v4.0 at screening. If a patient has a history of kidney disease or persistent proteinuria, a urine protein test will be performed on a random urine sample. If the result is normal then no additional testing is required. If the result is abnormal, a 24 hour urine will be collected to determine if proteinuria is less than Grade 3.
• •Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.
• •Any malabsorption condition that in the opinion of the investigator would significantly impact drug absorption.
• •Women who are pregnant or breast-feeding.
• •Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
• •Substance abuse, medical, psychological or social conditions that in the opinion of the investigator may interfere with the subject's participation in the study or evaluation of the study results.
• •Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) within 3 weeks of starting study treatment.
• •Concurrent use of another investigational drug or device during, or within 3 weeks of starting study treatment.
• •Major surgical procedure, open biopsy, or significant traumatic injury within 3 weeks before start of study medication.
• •Concurrent use of strong CYP3a4 inducers (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's Wort)
• •Concurrent use with strong inhibitors of CYP3A4 (e.g. clarithromycin, grapefruit juice, itraconazole, ketoconazole, nefazadone, posaconazole, telithromycin, and voriconazole)