Study of Nimotuzumab and Irinotecan as Second Line With Recurrent or Metastatic Gastric Adenocarcinoma

Study Overview
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Brief Summary
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The trial aims to evaluate the efficacy and safety of adding nimotuzumab to irinotecan after failure of first-line treatment in recurrent or metastatic gastric adenocarcinoma with overexpression of EGFR, and search for the effective biomarkers for nimotuzumab efficacy in gastric cancer.

Detailed Description
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The sample size was calculated using Simon's 2-stage design. The first stage require at least 4 or more out of 19 patients to have a confirmed partial or complete response (assuming P1 = 0.30, P0 = 0.10, with alpha = 0.05 and beta = 0.2) before proceeding to the second stage, in which additional 36 patients were needed. If a total of 15 or more patients achieve a confirmed objective response, then the primary end-point would have been met. The predicted response rate in this study is at least 30%. Blood and tissue samples are required to collect at baseline, response and disease progression.

Official Title
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Multi-center Phase II Trial of Nimotuzumab Plus Irinotecan in Patients With High EGFR Expression After Failure of First-line Treatment in Recurrent or Metastatic Gastric Adenocarcinoma（NIEGA）

Conditions
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Stomach Neoplasms

Intervention / Treatment
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* Drug: Irinotecan
* Drug: nimotuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced unresectable or recurrent gastric or gastroesophageal junction adenocarcinoma patients which meet the following criteria: Willing to sign ICF Above 18 years KPS score≥70 Expected survival time more than 90 days Subjects with EGFR overexpression (2+ or 3+ in IHC) With target lesions in spiral CT or MRI examination within 30 days Subjects who experienced disease progression during first line or within 6 months after the last dose of first line therapy. The first line regimen must have contained a 5-fluorouracil based agent ,platinum agent and Paclitaxel agent. Lab test of baseline meet following criteria Hemoglobin higher than 9.0g/dL Neutrophil higher than 1,500/mm3 PLT higher than 10.0 104/mm3 Bilirubin lower than 1.5 times of upper limit of normal range AST,ALT,ALP lower than 2.5 times of upper limit of normal range Creatinine lower than upper limit of normal range When patient has liver metastasis or bone metastasis, the value of AST,ALT,ALP could be within 5 times of upper limit of normal range Exclusion Criteria: Patients who have received irinotecan Patients who are allergic to irinotecan or nimotuzumab. Other active malignancy within the last 5 years Female patients who are in pregnancy or lactation and patients who are not willing to take contraception measures Investigator judge not eligible to this trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: irinotecan and nimotuzumab<br>Administration of irinotecan 180 mg/m2 IV once every 2 weeks and nimotuzumab 400 mg IV once weekly | Drug: Irinotecan<br>* 180 mg/m2 IV once every 2 weeks until radiographically documented tumour progression, unacceptable toxicity, or withdrawal of consent by the patient<br>Drug: nimotuzumab<br>* 400mg IV once weekly until radiographically documented tumour progression, unacceptable toxicity, or withdrawal of consent by the patient<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | CT/MRI will be performed every 2 cycles of treatment by RECIST 1.1.Overall Response Rate is defined as the proportion of subjects with CR or PR in the best overall response | From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival is defined as the time from the date of enrollment to the date of the death from any cause. | 3 years after first enrollment | 
| Progression free survival | Progression Free Survival is defined as the time from the date of enrollment to the date of progression or death from any cause | 3 years after first enrollment | 
| Disease control rate | Disease Control Rate is defined as the proportion of subjects with CR, PR or SD in the best overall response | From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 
| Safety | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 
| Potential predictive biomarkers of nimotuzumab |  | 3 years after first enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastric adenocarcinoma, EGFR, Irinotecan, Nimotuzumab, biomarker