A Study of Nimotuzumab Combinated With Gemcitabine in K-RAS Wild-type Locally Advanced and Metastatic Pancreatic Cancer
- Conditions
- Pancreatic Cancer
- Interventions
- Registration Number
- NCT02395016
- Lead Sponsor
- Biotech Pharmaceutical Co., Ltd.
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 90
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo and Gemcitabine Placebo 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. Nimotuzumab and Gemcitabine nimotuzumab 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. Nimotuzumab and Gemcitabine 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. Placebo and Gemcitabine 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.
- Primary Outcome Measures
Name Time Method Overall Survival（OS） up to 3 years 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).
- Secondary Outcome Measures
Name Time Method Time to Progression（TTP） up to 3 years 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.
Progression Free Survival（PFS） up to 3 years 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.
Clinical Benefit Response（CBR） every 8 weeks, up to 5.4 months 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.
Objective Response Rate（ORR） Once every eight weeks，up to 5.4 months 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.
Number of Participants With Adverse Events up to 75.2 months 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.
Disease Control Rate（DCR） Once every eight weeks，up to 5.4 months 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).
Trial Locations
- Locations (25)
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
First Affiliated Hospital of Bengbu Medical College
🇨🇳Bengbu, Anhui, China
Second Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
Beijing Union Medical College Hospital
🇨🇳Beijing, Beijing, China
Chinese Academy of Medical Sciences Cancer Hospital
🇨🇳Beijing, Beijing, China
PLA General Hospital (301 Hospital)
🇨🇳Beijing, Beijing, China
Affiliated Hospital of Military Medical Sciences
🇨🇳Beijing, Beijing, China
Fuzhou General Hospital of Nanjing Military Region
🇨🇳Fuzhou, Fujian, China
Fujian Provincial Tumor Hospital
🇨🇳Fuzhou, Fujian, China
Cancer Hospital of Harbin Medical University
🇨🇳Harbin, Heilongjiang, China
Jiangyin City People's Hospital
🇨🇳Jiangyin, Jiangsu, China
Jiangsu Province Tumor Hospital
🇨🇳Nanjing, Jiangsu, China
Second Affiliated Hospital of Dalian Medical University
🇨🇳Dalian, Liaoning, China
Shanghai Jiaotong University Affiliated Ruijin Hospital
🇨🇳Shanghai, Shanghai, China
Shanghai Fudan University Cancer Hospital
🇨🇳Shanghai, Shanghai, China
Shanghai Zhongshan Hospital, Fudan University
🇨🇳Shanghai, Shanghai, China
First People's Hospital Cancer Center, Shanghai Jiaotong University
🇨🇳Shanghai, Shanghai, China
Shanghai Huashan Hospital, Fudan University
🇨🇳Shanghai, Shanghai, China
Shanghai Changhai Hospital
🇨🇳Shanghai, Shanghai, China
Affiliated Xijing Hospital, Fourth Military Medical University
🇨🇳Xi'an, Shanxi, China
General Hospital of Chengdu Military Region
🇨🇳Chendu, Sichuan, China
Second Affiliated Hospital of Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
First Affiliated Hospital of Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Sir Run Run Shaw Hospital
🇨🇳Hangzhou, Zhejiang, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China