Pharmacokinetics Study of Nimotuzumab in Patients With Solid Tumors

NCT02395068 | Unknown Phase 1 DMC

• 1 other identifier: BT-PK-001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Solid Tumors

Keywords

Pharmacokinetics; Nimotuzumab; Safety; Effcacy; Irinotecan

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

• ORR（Objective Response Rate）

  The third weekend and Ninth weekend

• DCR（Disease Control Rate）

  The third weekend and Ninth weekend

• PFS（Progression Free Survival）

  The third weekend and Ninth weekend

Study Arms (3)

Single-dose PK

EXPERIMENTAL

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; Drug: irinotecan

Weekly fixed dose

EXPERIMENTAL

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

Drug: Nimotuzumab

Bioweekly fixed dose PK

EXPERIMENTAL

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; Drug: irinotecan

Interventions

Nimotuzumab DRUG

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.

Also known as: Taixinsheng

Bioweekly fixed dose PK; Single-dose PK; Weekly fixed dose

irinotecan DRUG

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

Also known as: CPT-11

Bioweekly fixed dose PK; Single-dose PK

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Biotech Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Cancer Institute & Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100000, China

Location

MeSH Terms

Interventions

nimotuzumab; Irinotecan

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Jinwan Wang, PhD，MD

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2015
• First Posted: March 20, 2015
• Study Start: November 1, 2012
• Primary Completion: November 1, 2014
• Study Completion: December 1, 2015
• Last Updated: August 19, 2015

Record last verified: 2012-10

Locations

CN (1)