The purpose of this study is to evaluate the efficacy and safety of recombinant anti-tumor and anti-virus protein for injection in treating patients with metastatic colorectal cancer after failure of second-line and more than second-line treatment.
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 1. Progression free survival were compared in both groups. 2. Disease control rate were compared in both groups. 3. Quality of life scores were compared in both groups. 4. Determine the safety and tolerance of recombinant anti-tumor and anti-virus protein for injection 5. 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
108
Recombinant anti-tumor and anti-virus protein for injection,10μg,im,twice per week for first 2 weeks, followed by 20μg, im, twice per week after 2 weeks
Recombinant anti-tumor and anti-virus protein for injection, 10μg/1mL,im,three times per week for first 2 weeks, followed by 20μg,im, three times per week after 2 weeks.
Saline Injection, 1mL, im,three times per week
307 Hospital of PLA
Beijing, Beijing Municipality, China
Overall survival (OS)
OS is defined as the length of time from random assignment to death or to last contact.
Time frame: every 8 weeks until death, the average OS is thought to be 4.5~6 months
Progression-free survival (PFS)
PFS is defined as the length of time from random assignment to disease progression or to death resulting from any cause other than the progress.
Time frame: every 6 weeks until disease progress, the estimate averge time is 2~3 months
Quality of life (QoL)
Quality of life is assessed using EORTC-C30 (the Quality of Life Questionnaire of the European Organisation for Research and Treatment of Cancer.)
Time frame: every 2 weeks in first 4 weeks and every 4 weeks after 4 weeks, it will last to the treatment end.
Adverse Events(AEs)
AEs are evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events v3.0.
Time frame: from informed consent form signed to 28 days after termination of administration.
pharmacodynamics
As the drug concentration is very low, and no commercialized kits for original drug test, So original drug will not detect. Mopterin and MxA protein (alternate index) levels in serum will be used as alternative targets for pharmacodynamic studies
Time frame: The first 2 weeks during 10ug dosage were given and the following 11weeks during 20ug dosage were given
Disease Control Rate
The disease control rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response + Stable Disease as best overall response according to radiological assessments (based on modified WHO criteria)
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Recombinant anti-tumor and anti-virus protein for injection, 10μg, im, three times per week for first week, followed by 20μg for two weeks, and followed by 30μg for a week, and followed a maintenance dose of 40μg, the frequency of administration is three times per week.
Time frame: every 6 weeks until disease progression