Title
Study of Gamma Interfereon in Metastatic Colorectal Carcinoma
Phase II Study of Gamma Interferon (IFN-γ) Added to Bolus + Infusional 5-Fluorouracil (5-FU) and Leucovorin (LV) +/- Bevacizumab (BV) in Metastatic Colorectal Carcinoma
Phase
Phase 2Lead Sponsor
National Cancer Institute (NCI)Study Type
InterventionalStatus
Completed Results PostedIndication/Condition
Colorectal CancerIntervention/Treatment
fluorouracil leucovorin bevacizumab interferon gamma-1b ...Study Participants
48The 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.
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.
Leucovorin 200mg/m^2 was administered over 2 hours on day 1 and day 2 of each cycle.
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.
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.
Patients in stratum 1 have not received prior chemotherapy in the metastatic setting.
Patients in stratum 2 have received 1-2 prior chemotherapy regimens in the metastatic setting.
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
| Event Type | Organ System | Event Term | Stratum 1 | Stratum 2 |
|---|
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.
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.
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.
