Colon Cancer
Conditions
Keywords
colon cancer, metastatic, vaccine
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
Interventions
DRUGchemotherapy 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
DRUGGI-4000
40 YU GI-4000 every 2 weeks Bevacizumab every 2 weeks
Sponsors
GlobeImmune
Georgetown University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
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 | 7 |
| GI-4000 and Bevacizumab maintenance with GI-4000 and bevacizumab for patients who have completed first-line chemotherapy
GI-4000: 40 YU GI-4000 every 2 weeks Bevacizumab every 2 weeks | 4 |
| Total | 11 |
Baseline characteristics
| Characteristic | Chemotherapy and GI-4000 | GI-4000 and Bevacizumab | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 4 Participants | 9 Participants |
| Age, Continuous | 48 years | 45 years | 45 years |
| Prior treatment status No prior therapy | 7 participants | 0 participants | 7 participants |
| Prior treatment status Prior 1st-line therapy | 0 participants | 4 participants | 4 participants |
| Region of Enrollment United States | 7 participants | 4 participants | 11 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 5 Participants | 1 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 7 | 4 / 4 |
| serious Total, serious adverse events | 2 / 7 | 0 / 4 |
Outcome results
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 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.
Time frame: 4 Months for patients who had undergone prior 1st-line therapy, and 10 months for previously untreated patients
Population: Patients with RAS mutant positive metastatic colorectal cancer (CRC), either newly diagnosed, or having completed first line therapy with an oxaliplatin or irinotecan plus fluoropyrimidine and bevacizumab containing regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemotherapy and GI-4000 | Number of Participants Alive and Free of Progression at 4 Months (Patients Who Have Undergone Prior Therapy) and 10 Months (Untreated Patients) | 4 participants |
| GI-4000 and Bevacizumab | Number of Participants Alive and Free of Progression at 4 Months (Patients Who Have Undergone Prior Therapy) and 10 Months (Untreated Patients) | 2 participants |