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

Colon Cancer Clinical Trial

Official title:

A Pilot Trial of GI-4000 Plus Bevacizumab and Either FOLOFOX or FOLFIRI in Patients With Newly Diagnosed Ras Mutant Positive Metastatic Colorectal Cancer or Patients With Ras Mutant Positive Colorectal Cancer Who Have Just Completed a First Line Therapy With an Oxaliplatin or Irinotecan Plus Fluoropyrimidine and Bevacizumab Containing Regimen

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01322815
• Other study ID #: GI-4000-05
• Status: Terminated
• Phase: Phase 2
• First received: March 23, 2011
• Last updated: March 12, 2015
• Start date: October 2010
• Est. completion date: December 2015

Study information

• Verified date: September 2014
• Source: Georgetown University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: December 2015
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colon Cancer

Intervention

Drug:
• chemotherapy and GI-4000
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
• GI-4000
40 YU GI-4000 every 2 weeks Bevacizumab every 2 weeks

Locations

Country	Name	City	State
United States	Georgetown University	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Georgetown University	GlobeImmune

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 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.	10 months	No