A Phase 2 Randomized, Open-Label Study of RRx-001 vs Regorafenib in Subjects With Metastatic Colorectal Cancer

Inclusion Criteria:

   - Histological or cytological documentation of adenocarcinoma of the colon or rectum;

   - Subject must have received at least oxaliplatin-, and irinotecan-based regimens with
   bevacizumab and with, cetuximab or panitumumab if KRAS wildtype and are refractory to
   irinotecan;

   - Subject has measurable disease by radiographic techniques (computerized tomography
   [CT] or magnetic resonance imaging [MRI]);

   - Subjects with a history of brain metastasis are eligible for the study as long as they
   meet all the following criteria: their brain metastases have been treated, they have
   no evidence of progression or hemorrhage after treatment, have been off dexamethasone
   for 4 weeks prior to first study drug administration, and have no ongoing requirement
   for dexamethasone or anti-epileptic drugs;

   - Life expectancy of at least 12 weeks

   - Subject's Eastern Cooperative Group (ECOG) performance status is 0 or 1;

   - Adequate organ function

   - Fertile subjects must use effective contraception during the course of the study and
   for 30 days following withdrawal from the study;

Exclusion Criteria:

   - Clinically significant cardiovascular disease;

   - Unresolved toxicity higher attributed to any prior therapy/procedure excluding
   alopecia, hypothyroidism and oxaliplatin- induced neurotoxicity ≤ Grade 2 for at least
   14 days;

   - Evidence or history of tendency or predisposition to active bleeding. Any hemorrhage
   or bleeding event of Grade 3 or higher within 4 weeks of start of study medication;

   - Symptoms or signs of active brain metastases;

   - History of an allergic reaction or intolerance to irinotecan

   - Hepatic encephalopathy

   - Cholangitis that required treatment or intervention within 4 weeks of study enrollment

   - Concurrent anticancer therapy or any cytotoxic therapy within 1 month prior to Day 1.
   Corticosteroid therapy is not allowed except on dosing days;

   - Subject has previously received regorafenib;

   - Clear contraindication for systemic corticosteroids (diabetes mellitus is not per se a
   clear contraindication);

   - Severe hypoalbuminemia (albumin < 3.0 g/dL);

   - Subjects who are pregnant or lactating or who are planning to become pregnant during
   the course of the study are excluded.