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

Phase 2

Terminated

• Conditions: Colon Cancer
• Interventions: Drug: GI-4000; Drug: chemotherapy and GI-4000

• Registration Number: NCT01322815
• Lead Sponsor: Georgetown University

Brief Summary

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

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

Study Timeline

• Study Start: 2010-10
• Study First Submitted: 2011-03-23
• Study First Submitted QC: 2011-03-23
• Study First Posted: 2011-03-25
• Primary Completion: 2014-09
• Study Completion: 2015-12
• Status Verified: 2016-02
• Results First Submitted: 2016-04-29
• Results First Submitted QC: 2016-07-06
• Last Update Submitted: 2016-07-06
• Results First Posted: 2016-08-15
• Last Update Posted: 2016-08-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 11

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GI-4000 and bevacizumab	GI-4000	maintenance with GI-4000 and bevacizumab for patients who have completed first-line chemotherapy
Chemotherapy and GI-4000	chemotherapy and GI-4000	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

Primary Outcome Measures

Name	Time	Method
Number of Participants Alive and Free of Progression at 4 Months (Patients Who Have Undergone Prior Therapy) and 10 Months (Untreated Patients)	4 Months for patients who had undergone prior 1st-line therapy, and 10 months for previously 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.

Trial Locations

Locations (1)

Georgetown University; 🇺🇸 Washington, District of Columbia, United States