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

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

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

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: nimotuzumab; Drug: Gemcitabine; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: shukui qin, MD, PHD; Phone Number: 025-80864541; Email: qinsk@csco.org.cn

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233004
      • First Affiliated Hospital of Bengbu Medical College
    • Hefei, Anhui, China, 230601
      • Second Affiliated hospital of Anhui Medical University
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100021
      • Chinese Academy of Medical Sciences Cancer Hospital
    • Beijing, Beijing, China, 100005
      • Beijing Union Medical College Hospital
    • Beijing, Beijing, China, 100039
      • PLA General Hospital (301 Hospital)
    • Beijing, Beijing, China, 100071
      • Affiliated Hospital of Military Medical Sciences
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Provincial Tumor Hospital
    • Fuzhou, Fujian, China, 350000
      • Fuzhou General Hospital of Nanjing Military Region
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150040
      • Cancer Hospital of Harbin Medical University
  • Jiangsu
    • Jiangyin, Jiangsu, China, 214400
      • Jiangyin City People's Hospital
    • Nanjing, Jiangsu, China, 210009
      • Jiangsu Province Tumor Hospital
  • Liaoning
    • Dalian, Liaoning, China, 116027
      • Second Affiliated Hospital of Dalian Medical University
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Shanghai Changhai Hospital
    • Shanghai, Shanghai, China, 200032
      • Shanghai Zhongshan Hospital, Fudan University
    • Shanghai, Shanghai, China, 200025
      • Shanghai Jiaotong University Affiliated Ruijin Hospital
    • Shanghai, Shanghai, China, 200032
      • Shanghai Fudan University Cancer Hospital
    • Shanghai, Shanghai, China, 200040
      • Shanghai Huashan Hospital, Fudan University
    • Shanghai, Shanghai, China, 200080
      • First People's Hospital Cancer Center, Shanghai Jiaotong University
  • Shanxi
    • Xi'an, Shanxi, China, 710032
      • Affiliated Xijing Hospital, Fourth Military Medical University
  • Sichuan
    • Chendu, Sichuan, China, 610083
      • General Hospital of Chengdu Military Region
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital
    • Hangzhou, Zhejiang, China, 310009
      • Second Affiliated Hospital of Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China, 310003
      • First Affiliated Hospital of Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nimotuzumab and Gemcitabine; 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; nimotuzumab,400mg/w，Intravenous infusion over 60 minutes,Until disease progression or intolerable toxicity or subjects ask to leave the test.; Other Names: Taixinsheng; Drug: Gemcitabine; 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.
Placebo Comparator: Placebo and Gemcitabine; 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; 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.; Other: Placebo; Placebo，400mg/w，Intravenous infusion over 60 minutes,Until disease progression or intolerable toxicity or subjects ask to leave the test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival（OS）	The primary endpoint was overall survival (OS, defined as from randomization to death due to any cause). We screened 90 pts (90 patients were allocated for treatment) from 480 pts, of whom 8 pts were excluded due to serious violation of the inclusion criteria: 7 pts with K-Ras mutants, 1 pt with gallbladder cancer. Finally, 82 pts were included in FAS. The primary end point was evaluated in the full analysis set (FAS; all eligible patients who received at least one dose of nimotuzumab/placebo and had one evaluation of efficacy).	up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Progression（TTP）	TTP, defined as from randomization to the first observation of disease progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	up to 3 years
Progression Free Survival（PFS）	PFS, defined as from randomization to disease progression or all-cause death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	up to 3 years
Objective Response Rate（ORR）	Objective response rate (ORR), including complete response (CR) and partial response (PR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions.	Once every eight weeks，up to 5.4 months
Disease Control Rate（DCR）	Disease control rate (DCR), including complete response (CR) and partial response (PR) and stable disease(SD). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT/MRI: CR, disappearance of all target lesions; PR, at least a 30% decrease in the sum of the longest diameter of target lesions. SD, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (PD, defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions).	Once every eight weeks，up to 5.4 months
Clinical Benefit Response（CBR）	The clinical benefit response(CBR)was evaluated every 8 weeks on the basis of the Burris criteria. CBR included pain (intensity of pain and consumption of analgesics), PS (performance status, evaluated according to KPS) and weight changes. Effective is defined as at least one positive improvement in the CBR index (pain, physical status or weight change) and no negative indicator is found, which can be rated as a clinical benefit case.	every 8 weeks, up to 5.4 months
Number of Participants With Adverse Events	Adverse Events as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	up to 75.2 months

Collaborators and Investigators

• Sponsor: Biotech Pharmaceutical Co., Ltd.
• Collaborators: Fudan University; NanJing PLA 81 Hospital
• Investigators: Principal Investigator: shukui qin, MD, PHD, 81th Hospital of PLA; Principal Investigator: jin li, MD, PHD, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): November 1, 2021

Study Registration Dates

• First Submitted: January 17, 2015
• First Submitted That Met QC Criteria: March 17, 2015
• First Posted (Estimated): March 20, 2015

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Nimotuzumab; Gemcitabine
• Other Study ID Numbers: BPL-Nim-PC-1