['colorectal cancer']
['irinotecan hydrochloride', 'vemurafenib']

        -  STEP I INITIAL REGISTRATION: BRAFV600E TESTING:

          -  Patients must have histologically or cytologically documented adenocarcinoma of the
             colon or rectum that is either metastatic, or locally advanced and unresectable

          -  Patients must have BRAFV600E mutant status documented by a Clinical Laboratory
             Improvements Amendments (CLIA) certified laboratory on a pathology report prior to
             Step 2 registration; use of an Food and Drug Administration (FDA)-approved test is
             preferred although other BRAF tests at a CLIA-certified laboratory may also be
             accepted; if a BRAFV600E mutation is known, then the patient must be registered to
             Step 2 Randomization immediately following Step 1 Initial Registration; if testing has
             not been performed locally, BRAFV600E testing must be completed by the central lab
             prior to Step 2 Randomization; if the specimen does not have a BRAFV600E mutation, the
             patient is ineligible for Step 2 Randomization

          -  Brain metastases are allowed if they have been adequately treated with radiotherapy or
             surgery and stable for at least 90 days prior to Step 1 Initial Registration; eligible
             patients should be neurologically asymptomatic and without corticosteroid treatment
             for at least 7 days prior to Step 1 Initial Registration

          -  Patients must have had one or two prior regimens of systemic chemotherapy for
             metastatic disease; prior treatment with irinotecan is allowed; a maintenance regimen
             of 5-fluorouracil or capecitabine, with or without bevacizumab, should not be counted
             as a separate line of treatment; prior treatment for metastatic disease is not
             required for patients who experienced disease recurrence during or within 6 months of
             completion of adjuvant chemotherapy

          -  Patients must not have been treated with any of the following prior to Step 2
             Randomization:

               -  Cetuximab, panitumumab, or any other monoclonal antibody against EGFR or
                  inhibitor of EGFR

               -  BRAF inhibitor including, but not limited to, vemurafenib or dabrafenib;
                  regorafenib is not considered a BRAF inhibitor for the purpose of determining
                  trial eligibility

               -  Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor
                  including, but not limited to, trametinib or selumetinib

          -  Previous chemotherapy, immunotherapy, or radiation therapy must have been completed at
             least 14 days prior to Step 1 Initial Registration and all toxicity must be resolved
             to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) grade 1
             (with the exception of CTCAE v4.0 grade 2 neuropathy) prior to Step 1 Initial
             Registration

          -  Patients must not have a tumor with a mutation detected in codons 12 or 13 in KRAS;
             patients must not have a tumor with a known mutation detected in codons 61, 117, or
             146 of KRAS or NRAS

          -  SPECIMEN SUBMISSION CRITERIA:

          -  Patients must have tumor (slides or block) available for submission for V600E BRAF
             testing

          -  Patients must have additional tumor available and be willing to submit tissue and
             blood samples

          -  SPECIMEN SUBMISSION CRITERIA REGULATORY CRITERIA:

          -  Patients or their legally authorized representative must be informed of the
             investigational nature of this study and must sign and give written informed consent
             in accordance with institutional and federal guidelines; for Step 1 Initial
             Registration of patients who have not yet submitted specimens for the central
             BRAFV600E testing, the appropriate consent form is the Step 1 Consent Form; for both
             Step 1 Initial Registration and Step 2 Randomization of patients whose BRAF mutation
             status is already known, the appropriate consent form is the Step 2 Consent Form

          -  STEP 2 RANDOMIZATION:

          -  Patients must have BRAFV600E mutation

          -  Patients must have measurable or non-measurable metastatic disease; computed
             tomography (CT) scans or magnetic resonance imaging (MRIs) used to assess all disease
             must have been completed within 28 days prior to Step 2 Randomization; CT scans or
             MRIs must be assessed and documented on the Baseline Tumor Assessment Form (Response
             Evaluation Criteria in Solid Tumors [RECIST] 1.1)

          -  Patients must have a Zubrod performance status of 0-1

          -  Absolute neutrophil count (ANC) >= 1,500/mcL

          -  Platelets >= 100,00/mcL

          -  Hemoglobin >= 9 g/dL

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x
             institutional upper limit of normal (IULN) or =< 5 x IULN if liver metastases are
             present

          -  Total bilirubin =< 1.5 x IULN

          -  Serum creatinine =< 1.5 x IULN within 14 days prior to Step 2 Randomization OR

          -  Calculated creatinine clearance > 60 ml/min; the serum creatinine value used in the
             calculation must have been obtained within 14 days prior to Step 2 Randomization

          -  Patients must have an electrocardiogram (ECG) within 14 days prior to Step 2
             Randomization

          -  Patients must have corrected QT (QTc) =< 500 msec

          -  Patients must not have a known history of Gilbert's Syndrome or known homozygosity for
             the UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1)*28 allele

          -  Patients must not have interstitial pneumonia or extensive symptomatic interstitial
             fibrosis of the lung

          -  Patients must not have an uncontrolled intercurrent illness including, but not limited
             to, active bleeding diathesis, uncontrolled infection/disorders, nonmalignant medical
             illnesses that are uncontrolled or whose control may be jeopardized by the treatment
             with the study therapy, or psychiatric illness/social situations which would limit
             compliance with study requirements

          -  Patients must be able to swallow pill/tablet and have no refractory nausea, vomiting,
             malabsorption, external biliary shunt, or significant small bowel resection that would
             preclude adequate absorption

          -  Patients must not be pregnant or nursing; women/men of reproductive potential must
             have agreed to use an effective contraceptive method while on study and for 30 days
             after study treatment; a woman is considered to be of "reproductive potential" if she
             has had menses at any time in the preceding 12 consecutive months; in addition to
             routine contraceptive methods, "effective contraception" also includes heterosexual
             celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy
             prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal
             ligation; however, if at any point a previously celibate patient chooses to become
             heterosexually active during the time period for use of contraceptive measures, he/she
             is responsible for beginning contraceptive measures

          -  No other prior malignancy is allowed except for the following: adequately treated
             basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
             stage I or II cancer from which the patient is currently in complete remission, or any
             other cancer from which the patient has been disease free for three years

          -  STEP 2 RANDOMIZATION REGULATORY CRITERIA:

          -  Patients or their legally authorized representative must be informed of the
             investigational nature of this study and must sign and give written informed consent
             in accordance with institutional and federal guidelines; for all patients, the
             appropriate consent form for this registration is the Step 2 Consent Form

          -  As a part of the OPEN registration process the treating institution's identity is
             provided in order to ensure that the current (within 365 days) date of institutional
             review board approval for this study has been entered in the system

          -  STEP 3 CROSSOVER REGISTRATION:

          -  Patients must have documented disease progression while on Arm 1 of this protocol; the
             follow-up tumor assessment form documenting disease progression must be submitted to
             Southwestern Oncology Group (SWOG) prior to Step 3

          -  Registration to Step 3 Crossover must be within 28 days of discontinuation of Arm 1
             protocol treatment; patients going off treatment for any other reason are not eligible

          -  ANC >= 1,500/mcL within 14 days prior to Step 3 registration

          -  Platelets >= 100,00/mcL within 14 days prior to Step 3 registration

          -  Hemoglobin >= 9 g/dL within 14 days prior to Step 3 registration

          -  AST and ALT =< 2.5 x institutional upper limit of normal (IULN) or =< 5 x IULN if
             liver metastases are present within 14 days prior to Step 3 registration

          -  Total bilirubin =< 1.5 x IULN within 14 days prior to Step 3 registration

          -  Serum creatinine =< 1.5 x IULN within 14 days prior to Step 3 registration OR

          -  Calculated creatinine clearance > 60 ml/min; the serum creatinine value used in the
             calculation must have been obtained within 14 days prior to Step 3 registration
      