Colorectal Cancer
Conditions
Keywords
Gamma Interferon, 5-FU, LV
Brief summary
The purpose of this study is to evalute the response and toxicity of metastatic colorectal cancer patients to the regimen of gamma interferon added to bolus and infusional 5-fluorouracil and leucovorin (GFL) with or without bevacizumab.
Interventions
DRUG5-Fluorouracil
5-FU bolus was administered at 400mg/m\^2 on day 1 and day 2 of each cycle. 5-FU at 600 mg/m\^2 infusion was administered over 22 hours on day 1 and day 2 of each cycle.
DRUGLeucovorin (LV)
Leucovorin 200mg/m\^2 was administered over 2 hours on day 1 and day 2 of each cycle.
DRUGGamma-Interferon-1b (IFN-γ)
Gamma-Interferon 150 mcg/m\^2 was administered by subcutaneous injection on day 1 of each cycle immediately before treatment with 5-FU and LV, and on day 3 of each cycle immediately after treatment with 5-FU and LV.
DRUGBevacizumab
Bevacizumab 5mg/kg was only added to the treatment regimen of patients in stratum 1 who demonstrated stable disease on imaging repeated prior to the 5th cycle of treatment. Bavacizumab was administered on day 4 of each cycle.
Sponsors
InterMune
Accelerated Community Oncology Research Network
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
* Metastatic colorectal cancer, histologically or cytologically confirmed * Age 18 or greater * Adequate hematologic function (ANC \> 1500, hemoglobin \> 10 g/dl, platelet count \> 100,000) * Adequate hepatic parameters (bilirubin \< 2.0, Alk. Phos \< 5 times normal, ALT \< 5 times normal) * Adequate renal function (creatinine \< 2.0) * Performance status ECOG 0-2 * 0-2 prior lines of chemotherapy for metastatic colorectal cancer are allowed. Prior 5-FU/LV or capecitabine allowed either in the adjuvant setting, or in the metastatic setting or both. * Absence of other serious concurrent medical illnesses * Evaluable or measurable disease for phase I; measurable disease only for phase II
Exclusion criteria
* Histologies other than adenocarcinoma * Previous grade 4 toxicity to 5-FU +/- LV or capecitabine * Uncontrolled brain metastases * Chronic diarrhea (greater than five bowel movements per day) * Previous chemotherapy or radiation therapy less than 4 weeks prior to study day 1 (less than 6 weeks for chemotherapy with Mitomycin or nitrosoureas) * Major surgery within 2 weeks before study entry * Known allergic sensitivity to leucovorin * Prior exposure to IFN-γ * Previous hematopoietic growth factor (e.g. epoetin alfa or darbepoietin less than 2 weeks prior to study day 1) * Pregnancy or breast feeding. Women of child-bearing potential must have a negative pregnancy test before the first dose. * Other co-existing malignancies or malignancies diagnosed within the last 5 years, with the exception of basal cell carcinoma or cervical cancer in situ * Inability to provide written and informed consent * Uncontrolled hypertension * History of deep venous thrombosis or CVA * Prior exposure to bevacizumab * Proteinuria \> 500 mg/24 hr
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Response (BR) | After every 4 cycles of treatment (approximately every 56 days for up to about 280 days) | BR is recorded from start of treatment until progressive disease (PD). Imaging was repeated by same technique after every 4 cycles of treatment. Response was evaluated per Response Evaluation Criteria In Solid Tumors (RECIST) guidelines version 1.0. Per RECIST v1.0 and CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of \>=20%; PD, increase in existing lesions or new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Early Response Rate (RR) (Stratum 1 Only) | After 4 cycles of treatment (approximately 56 days) | Early RR evaluated in stratum 1 to see if bevacizumab (bev) would be added to GFL treatment (tx). Patients with stable disease (SD) pre 5th cycle of tx had bev added. Response was evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0. Per RECIST and CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in sum of longest diameter (LD) of target lesions; SD, neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of \>=20%; Progressive Disease (PD), increase in existing lesions or new lesions. |
| Time to Progression | From date of study treatment start until date of first documented progression or date of death from any cause, whichever came first, assessed up to 15 months | Patients were censored if they did not progress, stopped particiaption due to an adverse event, or withdrew consent following the start of study treatment. Response was evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) guidelines version 1.0. Per RECIST v1.0, Progressive Disease (PD) is defined as a measurable increase in smallest diameter of any target or non-target lesion, or the appearance of new lesions, since baseline. |
Countries
United States
Participant flow
Recruitment details
One community oncology research site in the US within the ACORN Network participated in this study. Phase II enrollment started in February 2006 and was closed in December 2008.
Pre-assignment details
Informed consent was obtained from all subjects. All subjects underwent a screening period during which pre-study assessments were completed. Subjects were assigned to a stratum, based on whether or not they had received previous treatment in the metastatic setting, at the time of study enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Stratum 1 Patients in stratum 1 have not received prior chemotherapy in the metastatic setting. | 20 |
| Stratum 2 Patients in stratum 2 have received 1-2 prior chemotherapy regimens in the metastatic setting. | 28 |
| Total | 48 |
Baseline characteristics
| Characteristic | Stratum 2 | Stratum 1 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 9 Participants | 18 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 11 Participants | 30 Participants |
| Age Continuous | 62.32 years STANDARD_DEVIATION 10.13 | 62.75 years STANDARD_DEVIATION 12.05 | 62.50 years STANDARD_DEVIATION 10.85 |
| Region of Enrollment United States | 28 participants | 20 participants | 48 participants |
| Sex: Female, Male Female | 15 Participants | 9 Participants | 24 Participants |
| Sex: Female, Male Male | 13 Participants | 11 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 20 | 26 / 27 |
| serious Total, serious adverse events | 2 / 20 | 5 / 27 |
Outcome results
Primary
Best Response (BR)
BR is recorded from start of treatment until progressive disease (PD). Imaging was repeated by same technique after every 4 cycles of treatment. Response was evaluated per Response Evaluation Criteria In Solid Tumors (RECIST) guidelines version 1.0. Per RECIST v1.0 and CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of \>=20%; PD, increase in existing lesions or new lesions.
Time frame: After every 4 cycles of treatment (approximately every 56 days for up to about 280 days)
Population: The best response is the best response recorded from the start of treatment until disease progression. Imaging was repeated by same technique after every 4 cycles of treatment. Subjects in both strata were evaluated for this outcome.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stratum 1 | Best Response (BR) | Partial response (PR) | 6 Participants |
| Stratum 1 | Best Response (BR) | Progressive disease (PD) | 6 Participants |
| Stratum 1 | Best Response (BR) | Stable disease (SD) | 7 Participants |
| Stratum 1 | Best Response (BR) | Not evaluable (NE) | 1 Participants |
| Stratum 1 | Best Response (BR) | Complete response (CR) | 0 Participants |
| Stratum 2 | Best Response (BR) | Not evaluable (NE) | 4 Participants |
| Stratum 2 | Best Response (BR) | Complete response (CR) | 0 Participants |
| Stratum 2 | Best Response (BR) | Partial response (PR) | 3 Participants |
| Stratum 2 | Best Response (BR) | Stable disease (SD) | 15 Participants |
| Stratum 2 | Best Response (BR) | Progressive disease (PD) | 6 Participants |
Secondary
Early Response Rate (RR) (Stratum 1 Only)
Early RR evaluated in stratum 1 to see if bevacizumab (bev) would be added to GFL treatment (tx). Patients with stable disease (SD) pre 5th cycle of tx had bev added. Response was evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0. Per RECIST and CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in sum of longest diameter (LD) of target lesions; SD, neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of \>=20%; Progressive Disease (PD), increase in existing lesions or new lesions.
Time frame: After 4 cycles of treatment (approximately 56 days)
Population: Prior to the 5th cycle of treatment, early response rate was evaluated in patients in stratum 1 to assess whether bevacizumab would be added to the GFL treatment regimen. Stratum 1 patients with SD at this time point will have bevacizumab added to the regimen. Subjects in stratum 2 were not evaluated for this outcome.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stratum 1 | Early Response Rate (RR) (Stratum 1 Only) | Complete response (CR) | 0 Participants |
| Stratum 1 | Early Response Rate (RR) (Stratum 1 Only) | Partial response (PR) | 5 Participants |
| Stratum 1 | Early Response Rate (RR) (Stratum 1 Only) | Stable disease (SD) | 7 Participants |
| Stratum 1 | Early Response Rate (RR) (Stratum 1 Only) | Progressive disease (PD) | 6 Participants |
| Stratum 1 | Early Response Rate (RR) (Stratum 1 Only) | Not evaluable (NE) | 2 Participants |
Secondary
Time to Progression
Patients were censored if they did not progress, stopped particiaption due to an adverse event, or withdrew consent following the start of study treatment. Response was evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) guidelines version 1.0. Per RECIST v1.0, Progressive Disease (PD) is defined as a measurable increase in smallest diameter of any target or non-target lesion, or the appearance of new lesions, since baseline.
Time frame: From date of study treatment start until date of first documented progression or date of death from any cause, whichever came first, assessed up to 15 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stratum 1 | Time to Progression | 5.5263 Months |
| Stratum 2 | Time to Progression | 3.9145 Months |