Pharmacokinetics Study of Nimotuzumab in Patients With Solid Tumors

Sponsor

Biotech Pharmaceutical Co., Ltd. (Other)

Overall Status

Unknown status

CT.gov ID

NCT02395068

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Drug: Nimotuzumab Drug: irinotecan	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2012

Actual Primary Completion Date :

Nov 1, 2014

Anticipated Study Completion Date :

Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single-dose PK 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 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. Other Names: Taixinsheng Drug: irinotecan 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 Other Names: CPT-11
Experimental: Weekly fixed dose Set 4 dose groups for Nimotuzumab, namely 100,200,400,600mg. Each group administered once a week for 6 weeks.	Drug: Nimotuzumab 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. Other Names: Taixinsheng
Experimental: Bioweekly fixed dose PK 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 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. Other Names: Taixinsheng Drug: irinotecan 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 Other Names: CPT-11

Arm

Intervention/Treatment

Experimental: Single-dose PK

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

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.

Other Names:

Taixinsheng

Drug: irinotecan

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

Other Names:

CPT-11

Experimental: Weekly fixed dose

Set 4 dose groups for Nimotuzumab, namely 100,200,400,600mg. Each group administered once a week for 6 weeks.

Drug: Nimotuzumab

Other Names:

Taixinsheng

Experimental: Bioweekly fixed dose PK

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

Other Names:

Taixinsheng

Drug: irinotecan

Other Names:

CPT-11

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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