Pharmacokinetics Study of Nimotuzumab in Patients With Solid Tumors

Study Overview
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Brief Summary
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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
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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.

Official Title
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Pharmacokinetics Study of Nimotuzumab Single-dose and Multiple-dose in Combination With Irinotecan in Patients With Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: Nimotuzumab
* Drug: irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Confirmed by pathology and / or cytology diagnosis in patients with advanced solid tumors Failure of first-line or multi-line chemotherapy and be suitable for irinotecan therapy Age 18-70 years, both genders at enrollment ECOG 0 to 1 Adequate bone marrow function Recover from the toxicity of previous treatment 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 Male or female with fertility in the trial are willing to take contraceptive measures Estimated life expectancy of 3 months or greater All patients signed written informed consent Exclusion criteria: Have previously received EGFR-targeted therapy Current treatment on other effective programs Participated in other clinical trial within 4 weeks after enrollment Nervous system symptoms caused by brain metastases need to apply steroidal anti-edema medications to control Persistent uncontrollable diarrhea CTCAE 2 level and above (4-6 times daily) Complete or incomplete intestinal obstruction Need to drainage pleural effusion and ascites Drug addiction and other adverse long-term alcoholics, as well as AIDS patients Occurred myocardial infarction within 6 months Diagnosed with severe interstitial pneumonitis or pulmonary fibrosis by Chest CT 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 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 Uncontrollable seizures or loss of insight because of psychosis Female patient is pregnant, breastfeeding, or of childbearing potential but not take contraceptive measures Male patient who want his spouse to be pregnant during the trial Researchers believe that should not participate in this trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Single-dose PK<br>single dose of nimotuzumab (100、200、400、600mg), with 3 weeks observation. 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. | Drug: Nimotuzumab<br>* 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.<br>* Other names: Taixinsheng;Drug: irinotecan<br>* 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<br>* Other names: CPT-11;|
| Experimental: Weekly fixed dose<br>Set 4 dose groups for Nimotuzumab, namely 100,200,400,600mg. Each group administered once a week for 6 weeks. | Drug: Nimotuzumab<br>* 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.<br>* Other names: Taixinsheng;|
| Experimental: Bioweekly fixed dose PK<br>Nimotuzumab 600mg, administered once every 2 weeks for 8 weeks. Dosing regimens can be adjusted according to the results of preliminary experiments. 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 | Drug: Nimotuzumab<br>* 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.<br>* Other names: Taixinsheng;Drug: irinotecan<br>* 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<br>* Other names: CPT-11;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | up to 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety - AE measured by NCI CTCAE v 3.0 | 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. | Any adverse medical events occur from the beginning of receiving study drug to the end of treatment after 30 days | 
| ORR（Objective Response Rate） | Efficacy as measured by RECIST v1.1 | The third weekend and Ninth weekend | 
| DCR（Disease Control Rate） | Efficacy as measured by RECIST v1.1 | The third weekend and Ninth weekend | 
| PFS（Progression Free Survival） | Efficacy as measured by RECIST v1.1 | The third weekend and Ninth weekend | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Nimotuzumab, Safety, Effcacy, Irinotecan