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

Pancreatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02395016
• Other study ID #: BPL-Nim-PC-1
• Status: Completed
• Phase: Phase 3
• Start date: April 2015
• Est. completion date: November 2021

Study information

• Verified date: April 2024
• Source: Biotech Pharmaceutical Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: November 2021
• Est. primary completion date: November 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• nimotuzumab
nimotuzumab,400mg/w,Intravenous infusion over 60 minutes,Until disease progression or intolerable toxicity or subjects ask to leave the test.
• 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.

Locations

Country	Name	City	State
China	Affiliated Hospital of Military Medical Sciences	Beijing	Beijing
China	Beijing Cancer Hospital	Beijing	Beijing
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	First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui
China	General Hospital of Chengdu Military Region	Chendu	Sichuan
China	Second Affiliated Hospital of Dalian Medical University	Dalian	Liaoning
China	Fujian Provincial Tumor Hospital	Fuzhou	Fujian
China	Fuzhou General Hospital of Nanjing Military Region	Fuzhou	Fujian
China	First Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Second 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	Cancer Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Second Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	Jiangyin City People's Hospital	Jiangyin	Jiangsu
China	Jiangsu Province Tumor Hospital	Nanjing	Jiangsu
China	First People's Hospital Cancer Center, Shanghai Jiaotong University	Shanghai	Shanghai
China	Shanghai Changhai Hospital	Shanghai	Shanghai
China	Shanghai Fudan University Cancer Hospital	Shanghai	Shanghai
China	Shanghai Huashan Hospital, Fudan University	Shanghai	Shanghai
China	Shanghai Jiaotong University Affiliated Ruijin Hospital	Shanghai	Shanghai
China	Shanghai Zhongshan Hospital, Fudan University	Shanghai	Shanghai
China	Affiliated Xijing Hospital, Fourth Military Medical University	Xi'an	Shanxi

Sponsors (3)

Lead Sponsor	Collaborator
Biotech Pharmaceutical Co., Ltd.	Fudan University, NanJing PLA 81 Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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