Study of Gamma Interfereon in Metastatic Colorectal Carcinoma

Phase 2

Completed

Interventions: Drug: 5-Fluorouracil
Drug: Leucovorin (LV)
Drug: Gamma-Interferon-1b (IFN-γ)
Drug: Bevacizumab

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Stratum 1	Leucovorin (LV)	Patients in stratum 1 have not received prior chemotherapy in the metastatic setting.
Stratum 1	Gamma-Interferon-1b (IFN-γ)	Patients in stratum 1 have not received prior chemotherapy in the metastatic setting.
Stratum 1	Bevacizumab	Patients in stratum 1 have not received prior chemotherapy in the metastatic setting.
Stratum 2	Leucovorin (LV)	Patients in stratum 2 have received 1-2 prior chemotherapy regimens in the metastatic setting.
Stratum 2	Gamma-Interferon-1b (IFN-γ)	Patients in stratum 2 have received 1-2 prior chemotherapy regimens in the metastatic setting.
Stratum 1	5-Fluorouracil	Patients in stratum 1 have not received prior chemotherapy in the metastatic setting.
Stratum 2	5-Fluorouracil	Patients in stratum 2 have received 1-2 prior chemotherapy regimens in the metastatic setting.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.