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

Study Overview
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Brief Summary
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The purpose of this study is to test the safety of GI-4000 and see what effects (good and bad) it has against cancer over time. This study is also being done to measure the immune response to GI-4000. Study drug will be given in addition to a standard of care which is a standard therapy given to patients with your type of cancer (colon).

Detailed Description
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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 40 yeast units (YU) 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 yeast unit (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

Official Title
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A Pilot Trial of GI-4000 Plus Bevacizumab and Either FOLFOX or FOLFIRI in Patients With Ras Mutant Positive Metastatic Colorectal Cancer, Either Newly Diagnosed or Previously Treated.

Conditions
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Colon Cancer

Intervention / Treatment
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* Drug: chemotherapy and GI-4000
* Drug: GI-4000


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of metastatic colorectal cancer with a Ras mutation Measurable or evaluable disease No prior therapy fore metastatic disease except for group A: > 6 months since completion of adjuvant therapy and Group B: those patients who enroll just after completing bevacizumab plus FOLFOX or FOLFIRI Anticipated survival of at least 6 months Ambulatory with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Ability to maintain weight Normal organ and marrow function Women of child-bearing potential and men must agree to avoid pregnancy or fathering a child for the duration of study participation and for 6 months after the final scheduled study visit. Ability to understand and willingness to sign a written informed consent document Exclusion Criteria: Prior chemotherapy other than that listed in inclusion criteria Receiving any other investigational agent Known brain metastases, uncontrolled seizure disorders, encephalitis, or multiple sclerosis History of known hypersensitivity to S. cerevisiae, bevacizumab or any component of FOLFOX or FOLFIRI Concurrent and chronic therapy with corticosteroids or any other immunosuppressive drugs Uncontrolled hypertension, unstable angina, congestive heart failure, peripheral vascular disease, serious cardiac arrythmias requiring medication History of heart attack or stroke within 6 months before enrollment History of intra-abdominal abscess, abdominal fistula, gastrointestinal perforation, or active peptic ulcer disease Bleeding disorder or coagulopathy Serious non-healing wound, ulcer or bone fracture Major surgical procedure, open biopsy, or traumatic injury within 4 weeks prior to enrollment or anticipation of need for surgery during the study Known active infection with HIV, hepatitis B or C History of splenectomy History of Crohn's disease or ulcerative colitis History of organ transplantation Evidence of immunodeficiency or immune suppression Any Autoimmune disease Active infection Concurrent malignancy Pregnant or nursing

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy and GI-4000<br>Standard chemotherapy and bevacizumab 40 yeast units (YU) GI-4000 prior to initiation of chemotherapy and then intercycle 7 days after each chemotherapy cycle for up to 8 cycles. maintenance of GI-4000 injection and bevacizumab every 2 weeks | Drug: chemotherapy and GI-4000<br>* Standard chemotherapy and bevacizumab 40YU GI-4000 prior to initiation of chemotherapy and then intercycle 7 days after each chemotherapy cycle for up to 8 cycles. maintenance of GI-4000 injection and bevacizumab every 2 weeks<br>* Other names: avastin;|
| Experimental: GI-4000 and bevacizumab<br>maintenance with GI-4000 and bevacizumab for patients who have completed first-line chemotherapy | Drug: GI-4000<br>* 40 YU GI-4000 every 2 weeks Bevacizumab every 2 weeks<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Alive and Free of Progression at 4 Months (Patients Who Have Undergone Prior Therapy) and 10 Months (Untreated Patients) | Clinical benefit rate is defined as the proportion of patients alive and free of progression at 4 Months (Patients Who Have Undergone Prior Therapy) and 10 Months (Untreated Patients), 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. | 4 Months for patients who had undergone prior 1st-line therapy, and 10 months for previously untreated patients | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colon cancer, metastatic, vaccine