Solid Tumors
Conditions
Keywords
Pharmacokinetics, Nimotuzumab, Safety, Effcacy, Irinotecan
Brief summary
Nimotuzumab is an IgG1 humanized monoclonal antibody that recognized an epitope located in the extra cellular domain of the human epidermal growth factor receptor (EGFR), inhibiting tyrosine kinase activation. It has been approved to treat squamous cell carcinoma of head and neck (SCCHN), glioma and nasopharyngeal carcinoma in different countries. Currently, the registered clinical trials of Nimotuzumab combined with chemotherapy in advanced non-small cell lung cancer, colorectal cancer, esophageal cancer and glioma have been approved and are ongoing all over the investigators' country. The main purpose of this study is to evaluate the pharmacokinetic characteristics of Nimotuzumab combined with Irinotecan in patients with solid tumors.
Detailed description
This is a single-centered, non-randomized and open-labeled Clinical Pharmacokinetics Study of Nimotuzumab in patients with solid tumors. The test includes 3 dose groups, namely Single dose group, Multiple single-week dose group and Multiple bi week dose group, to evaluate the pharmacokinetic characteristics of Nimotuzumab combined with Irinotecan in patients with solid tumors.
Interventions
DRUGNimotuzumab
single dose of nimotuzumab (100、200、400、600mg), with 3 weeks observation；Set 4 dose groups for Nimotuzumab, namely 100,200,400,600mg. Each group administered once a week for 6 weeks；600mg, administered once every 2 weeks for 8 weeks.
DRUGirinotecan
Single-dose PK：1 week after nimotuzumb administration, irinotecan (CPT-11) will be given at a dose of 180 mg/m2 once every 2 weeks, 2 weeks a cycle. Bioweekly fixed dose PK：Nimotuzumab combined with irinotecan (180mg/m2), administering once every 2 weeks and considering 2 weeks as a period. If chemotherapy and Nimotuzumab are administered in the same day, chemotherapy should be infused after Nimotuzumab for at least 1h
Sponsors
Biotech Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Confirmed by pathology and / or cytology diagnosis in patients with advanced solid tumors 2. Failure of first-line or multi-line chemotherapy and be suitable for irinotecan therapy 3. Age 18-70 years, both genders at enrollment 4. ECOG 0 to 1 5. Adequate bone marrow function 6. Recover from the toxicity of previous treatment 7. At least one measurable site of disease as defined by at least 20mm in greatest dimension by CT or 10mm in greatest dimension by SCT/MRI 8. Male or female with fertility in the trial are willing to take contraceptive measures 9. Estimated life expectancy of 3 months or greater 10. All patients signed written informed consent
Exclusion criteria
1. Have previously received EGFR-targeted therapy 2. Current treatment on other effective programs 3. Participated in other clinical trial within 4 weeks after enrollment 4. Nervous system symptoms caused by brain metastases need to apply steroidal anti-edema medications to control 5. Persistent uncontrollable diarrhea CTCAE 2 level and above (4-6 times daily) 6. Complete or incomplete intestinal obstruction 7. Need to drainage pleural effusion and ascites 8. Drug addiction and other adverse long-term alcoholics, as well as AIDS patients 9. Occurred myocardial infarction within 6 months 10. Diagnosed with severe interstitial pneumonitis or pulmonary fibrosis by Chest CT 11. Severe or uncontrolled complications, such as infection required systemic treatment，fever（≥38℃），congestive heart failure，diabetes or hypertension that can not be controlled by drugs and other complications that may interfere with drug efficacy 12. Drug allergy（≥CTCAE 3.0）, such as shock or allergy symptoms, especially allergic to similar drugs in the past and severe hypersensitivity to polysorbate eighty-containing drugs 13. Uncontrollable seizures or loss of insight because of psychosis 14. Female patient is pregnant, breastfeeding, or of childbearing potential but not take contraceptive measures 15. Male patient who want his spouse to be pregnant during the trial 16. Researchers believe that should not participate in this trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of Nimotuzumab after administration of escalating single dosing and weekly fixed dosing in patients with solid tumors: Single dose：Tmax，Cmax， AUC，Vc，t1/2α，t1/2β，CL. Multiple dose：Tmax，Css-min，Css-max，Css-a，t1/2β，CL，AUCss，DF. | up to 9 weeks | The measure is a composite.The measure of single dose：Tmax，Cmax， AUC，Vc，t1/2α，t1/2β，CL. The measure of multiple dose：Tmax，Css-min，Css-max，Css-a，t1/2β，CL，AUCss，DF. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety - AE measured by NCI CTCAE v 3.0 | Any adverse medical events occur from the beginning of receiving study drug to the end of treatment after 30 days | Safety evaluations included adverse events and changes in laboratory data.Adverse events were descriptive statistics, lists the event occurred, the duration, severity, and drug relationship, as well as its outcome. |
| ORR（Objective Response Rate） | The third weekend and Ninth weekend | Efficacy as measured by RECIST v1.1 |
| DCR（Disease Control Rate） | The third weekend and Ninth weekend | Efficacy as measured by RECIST v1.1 |
| PFS（Progression Free Survival） | The third weekend and Ninth weekend | Efficacy as measured by RECIST v1.1 |
Countries
China
Outcome results
None listed