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

Georgetown University

Status and phase: Terminated; Phase 2

Conditions: Colon Cancer

Treatments: Drug: GI-4000; Drug: chemotherapy and GI-4000

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01322815

GI-4000-05

Details and patient eligibility

About

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).

Full 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

Enrollment: 11 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

11 participants in 2 patient groups

Chemotherapy and GI-4000

Experimental group

Description:

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

Treatment:

Drug: chemotherapy and GI-4000

GI-4000 and bevacizumab

Experimental group

Description:

maintenance with GI-4000 and bevacizumab for patients who have completed first-line chemotherapy

Treatment:

Drug: GI-4000