A Pilot Trial of GI-4000 Plus Bevacizumab and Either FOLOFOX or FOLFIRI

• Number of Participants alive and free of progression at 4 months(patients who have undergone prior therapy) and 10 months (untreated patients) [ Time Frame: 10 months ] [ Designated as safety issue: No ]
  clinical benefit rate is defined as the proportion of patients alive and free of progression at 10 months in group A or at 4 months in group B, assessed from first treatment with GI-4000. Progression is defined as CR (complete response) = disappearance of all target lesions; PR (partial response) = 30% decrease in the sum of the longest diameter of the target lesions; PD (progressive disease) = 20% increase in the sum of the longest diameter of the target lesions; or SD (stable disease) = small changes that do not meet the above criteria.
  
  

Subject visits will occur 1-4 weeks prior to initiation of GI-4000, then

• In newly diagnosed (Group A) patients, at every FOLFOX/FOLFIRI plus bevacizumab visit, bevacizumab and GI-4000 dosing visit, GI-4000 dosing visit and then quarterly after completion of therapy
• In patients with stable disease who have completed a first line therapy with an oxaliplatin or irinotecan plus fluoropyrimidine and bevacizumab containing regimen (Group B), at every bevacizumab and GI-4000 dosing visit, GI-4000 dosing visit and then quarterly after completion of therapy

Group A patients (N=26) will be enrolled into the study prior to the initiation of first line therapy with bevacizumab plus either FOLFOX (N=13) or FOLFIRI (N=13)

• Subjects will receive 1 40YU dose of GI-4000 prior to initiation of FOLFOX or FOLFIRI plus bevacizumab, then intercycle doses of GI-4000 will be given 7 days after each cycle while first line therapy is given (up to 8 cycles)
• After completion of first line therapy, subjects will enter the maintenance phase in which bevacizumab and GI-4000 will be given concurrently every 2 weeks for as long as therapy can be tolerated or until progression
• If a subject discontinues bevacizumab therapy due to intolerance, the subject will continue GI-4000 every 2 weeks until progression, intolerance or withdrawal from the study

Group B patients (N=26) with stable disease who have completed a first line therapy with an oxaliplatin or irinotecan plus fluoropyrimidine and bevacizumab containing regimen ) will enter the trial prior to receiving therapy with bevacizumab

• Subjects will receive 40 YU GI-4000 concurrently with each bevacizumab dose for as long as therapy can be tolerated or until progression
• If a subject discontinues bevacizumab therapy due to intolerance, the subject will continue GI-4000 every 2 weeks until progression, intolerance or withdrawal from the study