Recombinant Anti-tumor and Anti-virus Protein for Injection in Treatment of Metastatic Colorectal Cancer

Explanation for study design

The trial including two stages. The first is an exploration stage to decide delivery frequency and dose of study drug. It is single-blinded, subjects will be randomly divided into 4 groups with a 2:2:2:1 ratio. Study drug given twice per week or 3 times per, dose of the drug are from 20μg to 40μg. The sample size is 105, duration is 12 to 18 months. Based on preliminary efficacy and safety, the better dosage regimen will decided for the second stage.The second stage is double-blinded,subject will be randomly divided into treatment group or placebo group with 2:1 ratio and sample size is 600.

Primary purpose

To compare overall survival between study drug and placebo groups .

Secondary purpose

• Progression free survival were compared in both groups.
• Disease control rate were compared in both groups.
• Quality of life scores were compared in both groups.
• Determine the safety and tolerance of recombinant anti-tumor and anti-virus protein for injection
• Supplementary pharmacodynamics of recombinant anti-tumor and anti-virus protein for injection

Exploratory purpose Evaluate effects of recombinant anti-tumor and anti-virus protein for injection on the anti-tumor immunity, angiogenesis, apoptosis, cell proliferation, immune cells and cytokines levels.

Inclusion criteria

• Aged above 18 years.
• ECOG performance status 0, 1 or 2.
• Pathologically confirmed metastatic colorectal cancer.
• Failure of Second-Line or Above Treatment, and irinotecan- and oxaliplatin--containing regimens (If recurrence and metastasis occurred within 6 months after discontinuation of adjuvant chemotherapy, the adjuvant chemotherapy is considered to be first-line treatment). more than 4 weeks before enrollment after discontinuation of chemotherapy.
• Minimum of 4 weeks since any local radiotherapy or surgery for the control of symptoms or severe complications(local radiotherapy for the control of bone metastases is not the limit)，and adequately recovered from toxicities of any prior therapy).
• At least one measurable lesion according to the RECIST criteria that has not been previously local treated. Minimum indicator lesion size as follows: greater than or equal to 10 mm measured by spiral CT or NMR.
• The organ function is normal (laboratory test results came within 1 week before administration in the absence of ongoing supportive care): ANC ≥ 1.5 x 109/L, Platelets ≥ 80 x 109/L, Hgb ≥ 8.5 g/dL, serum total bilirubin ≤ 1.5 x upper limit of normal (ULN), and serum AST and ALT ≤ 2.5 x ULN(≤ 5 x ULN if liver metastases), serum creatinine ≤1.5 x ULN.
• Have been fully aware of the study and voluntarily signed the informed consent.
• Life expectancy of at least 3 months.

Exclusion criteria

• Pregnancy or breast-feeding women or women who may be pregnant were positive drug test before administration.
• Patient of child-bearing potential(male or less than 1 year postmenopausal women) were reluctant to take contraceptive measures.
• Patient who were allergic to Interferon-α or who had interferon-α antibody.
• Patients with uncontrolled central nervous system (CNS) metastases.
• Patient with any other Malignant tumors within five years (except for a complete cure of carcinoma in situ of the cervix or basal cell cancer or squamous cell skin cancer).
• Patient with Clinically uncontrolled active infection such as acute pneumonia, active hepatitis B, etc.
• Patient associated with Significant Systemic illness including, but not limited to, the following: cerebrovascular disease, uncontrolled diabetes, uncontrolled hypertension, acute myocardial infarction, unstable angina, Congestive heart failure ,serious dysrhythmias, metabolic diseases, thrombosis or thromboembolic events occurred(including transient ischemic attack) in the last 6 months.
• Patient with serious autoimmune diseases in the past or at present, such as systemic lupus erythematosus, rheumatoid arthritis, thyroiditis, etc.
• Patient with ascites, pleural and pericardial effusion that cannot be controlled by drainage or symptomatic treatment.
• Investigator think Patient is not appropriate to participate in this trial for any clinical or laboratory abnormalities, or patient with any grade ≥ 2 toxicity according to NCI CTC AE 3.0 standard .
• Patient who also are accepting other systemic anti-tumor therapy (local radiotherapy for the control of bone metastases is not the limit)), in this study received 4 weeks before the start of drug treatment of other tests.
• Patient who had serious psychological or psychiatric disorder or Drug addiction or alcohol dependence.
• Patient who are estimated to be lack of compliance in this study.
• Patient with acute or subacute intestinal obstruction.