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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
GlobeImmune
Information provided by (Responsible Party):
Georgetown University
ClinicalTrials.gov Identifier:
NCT01322815
First received: March 23, 2011
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

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).


Condition Intervention Phase
Colon Cancer
Drug: chemotherapy and GI-4000
Drug: GI-4000
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Georgetown University:

Primary Outcome Measures:
  • Number of Participants alive and free of progression at 4 months(patients who have undergone prior therapy) and 10 months (untreated patients) [ Time Frame: 10 months ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 52
Study Start Date: October 2010
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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

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

Other Names:
  • 5-FU, leucovorin. oxaliplatin
  • 5-FU, leucovorin, irinotecan
  • avastin
Experimental: GI-4000 and bevacizumab
maintenance with GI-4000 and bevacizumab for patients who have completed first-line chemotherapy
Drug: GI-4000
40 YU GI-4000 every 2 weeks Bevacizumab every 2 weeks
Other Name: Avastin

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 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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01322815

Locations
United States, District of Columbia
Georgetown University
Washington, District of Columbia, United States, 20007
Sponsors and Collaborators
Georgetown University
GlobeImmune
Investigators
Principal Investigator: John L Marshall, MD Georgetown University
  More Information

No publications provided

Responsible Party: Georgetown University
ClinicalTrials.gov Identifier: NCT01322815     History of Changes
Other Study ID Numbers: GI-4000-05
Study First Received: March 23, 2011
Last Updated: August 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Georgetown University:
colon cancer
metastatic
vaccine

Additional relevant MeSH terms:
Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Leucovorin
Bevacizumab
Oxaliplatin
Irinotecan
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014