
    slow accrual
  
['kras and nras wild-type colorectal cancer']
['regorafenib + panitumumab']

        Inclusion Criteria:

          -  Histological diagnosis of un-resectable or metastatic colorectal cancer which is KRAS
             and NRAS mutation negative (wild-type). Patients with any known mutation in KRAS or
             NRAS codons 12, 13, 59, 61, 117 or 146 will be excluded. Mutations of KRAS and NRAS
             codons not listed above are allowed. Biopsy of metastatic lesion is not required.

          -  Patients must show signs of progression (by imaging, or tumor marker elevation) after
             being treated with a first line or greater treatment for their un-resectable or
             metastatic colorectal cancer.

          -  Age 18 years or older.

          -  ECOG Performance Status 0-1

          -  Subjects must be able to understand and be willing to sign the written informed
             consent form. A signed informed consent form must be appropriately obtained prior to
             the conduct of any trial-specific procedure.

          -  Acute toxic effects of all prior treatment have resolved to NCI-CTCAE v4.0 less than
             or equal to Grade 1 or baseline prior to beginning treatment. Alopecia (any grade) is
             allowed. Peripheral neuropathy less than or equal to Grade 2 is allowed.

          -  Adequate bone marrow, renal and liver function as assessed by protocol laboratory
             requirements

          -  Women of childbearing potential must have a negative serum pregnancy test performed
             within 7 days prior to the start of study drug. Post-menopausal women (defined as no
             menses for at least 1 year) and surgically sterilized women are not required to
             undergo a pregnancy test.

          -  Subjects (men and women) of childbearing potential must agree to use adequate
             contraception beginning at the signing of the ICF until at least 3 months after the
             last dose of study drug. Highly effective contraception must be used (e.g. male condom
             with spermicidal, diaphragm with spermicidal, intra-uterine device) must be used by
             both sexes.

          -  Subject must be able to swallow medication.

          -  Measurable disease at screening by RECIST 1.1 criteria

        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)
      