Pharmacokinetics Study of Nimotuzumab in Patients With Solid Tumors

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

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.

Study Overview

• Status: Unknown
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: Nimotuzumab; Drug: irinotecan

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 Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Cancer Institute & Hospital, Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Biotech Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Jinwan Wang, PhD，MD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): November 1, 2014
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: February 28, 2015
• First Submitted That Met QC Criteria: March 19, 2015
• First Posted (Estimate): March 20, 2015

Study Record Updates

• Last Update Posted (Estimate): August 19, 2015
• Last Update Submitted That Met QC Criteria: August 17, 2015
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Irinotecan; Nimotuzumab; Effcacy
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Topoisomerase I Inhibitors; Irinotecan; Nimotuzumab
• Other Study ID Numbers: BT-PK-001