Clinical trial NCT01322815: A Pilot Trial of GI-4000 Plus Bevacizumab and Either FOLFOX or FOLFIRI
Official title: 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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Colon Cancer
Keywords: colon cancer
metastatic
vaccine
Lead sponsor: Georgetown University
Sponsor class: OTHER
Collaborators: name: GlobeImmune
First posted: 2011-03-25
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Alive and Free of Progression at 4 Months (Patients Who Have Undergone Prior Therapy) and 10 Months (Untreated Patients)
timeFrame: 4 Months for patients who had undergone prior 1st-line therapy, and 10 months for previously untreated patients
Secondary outcomes:
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
Study officials:
affiliation: Georgetown University
name: John L Marshall, MD
role: PRINCIPAL_INVESTIGATOR
References: