A Study of Nimotuzumab Combinated With Gemcitabine in K-RAS Wild-type Locally Advanced and Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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Nimotuzumab is a humanized monoclonal antibody against epidermal growth factor receptor (EGFR). Clinical trials are ongoing globally to evaluate Nimotuzumab in different indications. Nimotuzumab has been approved to treat squamous cell carcinoma of head and neck (SCCHN), glioma and nasopharyngeal carcinoma in different countries.The clinical phase Ⅲ trial designed to assess overall survival（OS）of the combination of Nimotuzumab administered concurrently with Gemcitabine in patients with RAS wild type of locally advanced or metastatic pancreatic cancer

Detailed Description
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Nimotuzumab is a humanized monoclonal antibody against epidermal growth factor receptor (EGFR). Clinical trials are ongoing globally to evaluate Nimotuzumab in different indications. Nimotuzumab has been approved to treat squamous cell carcinoma of head and neck (SCCHN), glioma and nasopharyngeal carcinoma in different countries.The clinical phase Ⅲ trial designed to assess overall survival（OS）of the combination of Nimotuzumab administered concurrently with Gemcitabine in patients with RAS wild type of locally advanced or metastatic pancreatic cancer.Secondary objectives include time to progression（TTP）,progression-free survival（PFS）,Objective Response Rate（ORR）,Disease Control Rate（DCR）,Clinical Benefit Response（CBR）and safety.

Official Title
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A Prospective, Randomized, Controlled, Double-blind, Multi-center Clinical Study of Nimotuzumab Combinated With Gemcitabine Contrast to Placebo Combinated With Gemcitabine in K-RAS Wild-type,Locally Advanced and Metastatic Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: nimotuzumab
* Drug: Gemcitabine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age:18-75 years old KPS≥60 Histological or cytological diagnosis that are unsuitable for radical radiotherapy or surgical treatment of locally advanced or metastatic pancreatic adenocarcinoma (≥6 months to the last adjuvant chemotherapy) Has at least one objective measurable lesion can be evaluated according to Response Evaluation Criteria in Solid Tumors1.1(Helical CT examination of the longest diameter of target lesions≥10mm, such as lymph node metastasis only need the shortest path ≥15mm) Life expectancy ≥12 weeks K-RAS tumor tissue detected as the wild-type Aspartate transaminase（AST）/aminotransferase（ALT）≤2.5×ULN，AST /ALT≤5×ULN（if liver metastases）；Total bilirubin≤2×ULN，Total bilirubin≤3×ULN（if liver metastases）；Absolute neutrophil count≥1.5×109/L；Blood platelet≥100×109/L；Hemoglobin≥90 g/L；Creatinine clearance≥60ml/min Volunteered to participate this study, written informed consent and has a good compliance Patients of childbearing age and their spouses are willing to take contraceptive measures Exclusion Criteria: Before this study had received the following treatments：As a means of anti-tumor palliative chemotherapy and molecular targeted therapy.Target lesion had received radiotherapy without progression.within 4 weeks or be participating in clinical trials of other therapeutic/ interventionist clinical trial. Undergone major surgery within 4 weeks. The brain metastasis or leptomeningeal metastasis. Has a history of malignancy other than the pancreatic cancer (except for the cured cervix in situ or basal cell carcinoma, and a five-year cure other cancers). The merger has symptoms of ascites and requires clinical treatment. Accompanied by other serious disease, including but not limited:Congestive heart failure which is difficult to control (NYHA III or IV), Unstable angina, Poorly controlled arrhythmia, Uncontrolled moderate to severe hypertension(systolic blood pressure（SBP）>160 mm Hg or diastolic blood pressure（DBP）>100 mm Hg).Active infection.Diabetes which is difficult to control.Has mental illness which impacts the informed consent and / or compliance program.HIV infection.There is serious illness that other researchers consider is unsuitable to participate this study. Known allergy to anti-EGFR antibody formulations.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nimotuzumab and Gemcitabine<br>nimotuzumab,400mg/w，Intravenous infusion over 60 minutes,Until disease progression or intolerable toxicity or subjects ask to leave the test. Gemcitabine，1000mg/m2，Intravenous infusion over 30 minutes,Once every three weeks, rest one week (d1,8,15; q28d), Every 4 weeks for a period,Until disease progression or intolerable toxicity or subjects ask to leave the test. | Drug: nimotuzumab<br>* nimotuzumab,400mg/w，Intravenous infusion over 60 minutes,Until disease progression or intolerable toxicity or subjects ask to leave the test.<br>* Other names: Taixinsheng;Drug: Gemcitabine<br>* Gemcitabine，1000mg/m2，Intravenous infusion over 30 minutes,Once every three weeks, rest one week (d1,8,15; q28d), Every 4 weeks for a period,Until disease progression or intolerable toxicity or subjects ask to leave the test.<br>|
| Placebo Comparator: Placebo and Gemcitabine<br>placebo,400mg/w，Intravenous infusion over 60 minutes,Until disease progression or intolerable toxicity or subjects ask to leave the test. Gemcitabine，1000mg/m2，Intravenous infusion over 30 minutes,Once every three weeks, rest one week (d1,8,15; q28d), Every 4 weeks for a period,Until disease progression or intolerable toxicity or subjects ask to leave the test. | Drug: Gemcitabine<br>* Gemcitabine，1000mg/m2，Intravenous infusion over 30 minutes,Once every three weeks, rest one week (d1,8,15; q28d), Every 4 weeks for a period,Until disease progression or intolerable toxicity or subjects ask to leave the test.<br>Other: Placebo<br>* Placebo，400mg/w，Intravenous infusion over 60 minutes,Until disease progression or intolerable toxicity or subjects ask to leave the test.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival（OS） |  | up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression（TTP） |  | up to 3 years | 
| Progression Free Survival（PFS） |  | up to 3 years | 
| Objective Response Rate（ORR） | Appeared efficacy from the beginning until proven disease progression | Once every eight weeks，up to 5.4 months | 
| Disease Control Rate（DCR） | The number of cases in remission after being treated and the disease stabilized accounts the total percentage of the number of evaluable patients | Once every eight weeks，up to 5.4 months | 
| Clinical Benefit Response（CBR） | Only evaluated the symptomatic patients in the study | Once a week,up to 5.4 months | 
| To determine the safety of the treatment with Nimotuzumab and Gemcitabine (NCI Common Terminology Criteria for Adverse Events v4.03) |  | Any adverse medical events occur from the beginning of receiving study drug to the end of treatment after 30 days |