Study of Gamma Interfereon in Metastatic Colorectal Carcinoma

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: 5-Fluorouracil
* Drug: Leucovorin (LV)
* Drug: Gamma-Interferon-1b (IFN-γ)
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stratum 1<br>Patients in stratum 1 have not received prior chemotherapy in the metastatic setting. | Drug: 5-Fluorouracil<br>* 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.<br>* Other names: 5-FU;Drug: Leucovorin (LV)<br>* Leucovorin 200mg/m^2 was administered over 2 hours on day 1 and day 2 of each cycle.<br>* Other names: folinic acid;Drug: Gamma-Interferon-1b (IFN-γ)<br>* 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.<br>* Other names: Actimmune;Drug: Bevacizumab<br>* 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.<br>* Other names: Avastin;|
| Experimental: Stratum 2<br>Patients in stratum 2 have received 1-2 prior chemotherapy regimens in the metastatic setting. | Drug: 5-Fluorouracil<br>* 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.<br>* Other names: 5-FU;Drug: Leucovorin (LV)<br>* Leucovorin 200mg/m^2 was administered over 2 hours on day 1 and day 2 of each cycle.<br>* Other names: folinic acid;Drug: Gamma-Interferon-1b (IFN-γ)<br>* 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.<br>* Other names: Actimmune;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | After every 4 cycles of treatment (approximately every 56 days for up to about 280 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | After 4 cycles of treatment (approximately 56 days) | 
| 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. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gamma Interferon, 5-FU, LV