Study of CMAB009 to Treat KRAS Wild Type Metastatic Colorectal Cancer (CRC009)
Primary Purpose
Metastatic Colorectal Cancer
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
CMAB009 plus Irinotecan
Irinotecan-only and sequential-CMAB009
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring KRAS wild-type, Metastatic Colorectal Cancer, CMAB009 Plus Irinotecan, Phase II/III
Eligibility Criteria
Inclusion Criteria:
- histologically confirmed metastatic colorectal adenocarcinoma
- KRAS wild-type tumors, EGFR-expressing or EGFR-nonexpressing by immunohistochemistry;
- has measurable lesion, at least 1cm in diametre by CT or MRI, at least 2cm diametre by physical examination or other iconography
- ECOG performance status 0 to 1
- Failure (disease progression/discontinuation due to toxicity) of fluoropyrimidine and oxaliplatin treatment,stop at least one month thereafter, irinotecan-naïve
Exclusion Criteria:
- Previous irinotecan or anti-EGFR therapies
- hematologic function: hemoglobin, less than 90g per liter; neutrophil count, less than 1500 per cubic millimeter; and platelet count, less than 100,000 per cubic millimeter
- liver function: bilirubin, more than 1.0 times the upper limit of normal; aspartate aminotransferase and alanine aminotransferase, more than 5.0 times and 2.5 times the upper limit of normal with hepatic metastasis or not
- Renal function: serum creatinine, more than 1.5 times the upper limit of normal
- Patients with symptomatic central nervous system metastases
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
CMAB009 plus Irinotecan
Irinotecan-only and sequential-CMAB009
Arm Description
Outcomes
Primary Outcome Measures
Overall response rate
Tumor response was evaluated every 6 weeks and confirmed at least 4 weeks later
Secondary Outcome Measures
Progression-free Survival
The study was designed to evaluate the PFS as second end point, progression-free survival is defined as the period from date of randomization to date of disease progression
Full Information
NCT ID
NCT01550055
First Posted
March 7, 2012
Last Updated
April 8, 2019
Sponsor
Shanghai Zhangjiang Biotechnology Limited Company
Collaborators
Shanghai Biomabs Pharmaceutical Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT01550055
Brief Title
Study of CMAB009 to Treat KRAS Wild Type Metastatic Colorectal Cancer
Acronym
CRC009
Official Title
CMAB009 Plus Irinotecan Versus Irinotecan-only as Second-line Treatment After Fluoropyrimidine and Oxaliplatin Failure in KRAS Wild-type Metastatic Colorectal Cancer Patients: Prospective, Open-label, Randomized, Phase II/III Trial
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
May 31, 2009 (Actual)
Primary Completion Date
December 23, 2012 (Actual)
Study Completion Date
July 23, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Zhangjiang Biotechnology Limited Company
Collaborators
Shanghai Biomabs Pharmaceutical Co., Ltd.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary purpose of this study is to evaluate the clinical response and safety of CMAB009 plus irinotecan versus irinotecan-only as second-line treatment after fluoropyrimidine and oxaliplatin failure in KRAS wild-type metastatic colorectal cancer patients
Detailed Description
CMAB009 is a recombinant, human/mouse chimeric monoclonal antibody (mAb) that binds specifically to the extracellular domain of EGFR. It is composed of the Fv regions of a murine anti-EGFR antibody with human IgG1 heavy and k light chain constant regions and it is expressed by Chinese hamster ovary cells. It has the same amino acid sequence as cetuximab (C225, Erbitux®) , but it has slightly different abilities for glycosylation and other post-translational modifications, and it is developed by Shanghai Zhangjiang Biotechnology Limited Company and produced by Biomabs. Phase I study results suggest that CMAB009 showed well-tolerated safety profile and primary efficacy. This multicenter, open-label study was to determine whether adding CMAB009 to irinotecan increased the response rate and prolongs survival in patients with KRAS wild-type metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine and oxaliplatin.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
KRAS wild-type, Metastatic Colorectal Cancer, CMAB009 Plus Irinotecan, Phase II/III
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
512 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CMAB009 plus Irinotecan
Arm Type
Experimental
Arm Title
Irinotecan-only and sequential-CMAB009
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
CMAB009 plus Irinotecan
Other Intervention Name(s)
YiMaiLin for irinotecan
Intervention Description
Combined with irinotecan 180 mg/m2 every 2 weeks, CMAB009 400 mg/m2 day 1 followed by 250 mg/m2 weekly till disease progression
Intervention Type
Drug
Intervention Name(s)
Irinotecan-only and sequential-CMAB009
Other Intervention Name(s)
YiMaiLin for irinotecan
Intervention Description
First, irinotecan 180 mg/m2 every 2 weeks till PD occured, discontinue it; then, CMAB009 400 mg/m2 day 1 followed by 250 mg/m2 weekly till disease progression.
Primary Outcome Measure Information:
Title
Overall response rate
Description
Tumor response was evaluated every 6 weeks and confirmed at least 4 weeks later
Time Frame
Time to progression, assessed up to two years
Secondary Outcome Measure Information:
Title
Progression-free Survival
Description
The study was designed to evaluate the PFS as second end point, progression-free survival is defined as the period from date of randomization to date of disease progression
Time Frame
Time to progression, assessed up to two years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
histologically confirmed metastatic colorectal adenocarcinoma
KRAS wild-type tumors, EGFR-expressing or EGFR-nonexpressing by immunohistochemistry;
has measurable lesion, at least 1cm in diametre by CT or MRI, at least 2cm diametre by physical examination or other iconography
ECOG performance status 0 to 1
Failure (disease progression/discontinuation due to toxicity) of fluoropyrimidine and oxaliplatin treatment,stop at least one month thereafter, irinotecan-naïve
Exclusion Criteria:
Previous irinotecan or anti-EGFR therapies
hematologic function: hemoglobin, less than 90g per liter; neutrophil count, less than 1500 per cubic millimeter; and platelet count, less than 100,000 per cubic millimeter
liver function: bilirubin, more than 1.0 times the upper limit of normal; aspartate aminotransferase and alanine aminotransferase, more than 5.0 times and 2.5 times the upper limit of normal with hepatic metastasis or not
Renal function: serum creatinine, more than 1.5 times the upper limit of normal
Patients with symptomatic central nervous system metastases
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yuankai Shi, M.D.
Organizational Affiliation
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
B C Mei
Organizational Affiliation
Peking Union Medical College Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
B Li
Organizational Affiliation
Chinese PLA Affiliated Central Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
X J Ming
Organizational Affiliation
Affiliated Hospital of Chinese PLA Military Academy of Medical Science
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
B Yi
Organizational Affiliation
TianJin Medical University Affiliated Cancer Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Y Qiang
Organizational Affiliation
NanKai University Affiliated Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
L Wei
Organizational Affiliation
HeBei Medical University Fouth Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
L Y Peng
Organizational Affiliation
Chinese Medical University First Affiliated Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
W B Cheng
Organizational Affiliation
Jinan Military Central Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
W Z Hai
Organizational Affiliation
Shandong Provincal Cancer Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Y S Ying
Organizational Affiliation
Tongji Medical College of Huazhong University of Science and Technology
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
L Yi
Organizational Affiliation
Hunan Provincal Cancer Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
C Y Gui
Organizational Affiliation
Fujian Provincal Cancer Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
W L Wei
Organizational Affiliation
Shanghai Jiaotong University Affiliated First People's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Z Jun
Organizational Affiliation
Shanghai Jiaotong University Affiliated Ruijin Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
H C Hong
Organizational Affiliation
Central South University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
OY Xuenong
Organizational Affiliation
Fuzhou Central Hospital of Nanjing Military Command
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
L Jin
Organizational Affiliation
Fudan University Affiliated Cancer Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Z Y Ping
Organizational Affiliation
Zhejiang Provincal Cancer Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
H X Hua
Organizational Affiliation
Guangxi Medical University Affiliated Cancer Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
L R Cheng
Organizational Affiliation
Nanfang Medical University Affiliated Nanfang Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
L Y Hong
Organizational Affiliation
Zhongshan University Affliated Cancer Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
T Min
Organizational Affiliation
Suzhou University Affiliated First Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Z Z Xiang
Organizational Affiliation
Suzhou University Affiliated Second Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
C Ying
Organizational Affiliation
Jilin Provincal Cancer Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
F J Feng
Organizational Affiliation
Jiangsu Provincal Cancer Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Q S Qui
Organizational Affiliation
Chinese PLA Affiliated 81 Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
J Bin
Organizational Affiliation
Shanghai Jiaotong University Affiliated Third People's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Z R Sheng
Organizational Affiliation
First Affiliated Hospital Bengbu Medical College
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
M G Xin
Organizational Affiliation
Nantong Medical College Affiliated Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
S G Ping
Organizational Affiliation
Anhui Medical University Affiliated First Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
D W Chao
Organizational Affiliation
The Fourth Military University Affiliated First Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
L H Jie
Organizational Affiliation
The Third Military University Affiliated First Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
X Ying
Organizational Affiliation
Chongqing University Cancer Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
F Min
Organizational Affiliation
Chongqing First People's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
B Feng
Organizational Affiliation
Sichuan University Huaxi Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
W D Lin
Organizational Affiliation
Sichuan Provincal People's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Z W Hua
Organizational Affiliation
Gansu Provincal Cancer Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
C Hong
Organizational Affiliation
Kunming Central Hospital of Chengdu Military Command
Official's Role
Principal Investigator
12. IPD Sharing Statement
Citations:
PubMed Identifier
31126331
Citation
Shi Y, Li J, Xu J, Sun Y, Wang L, Cheng Y, Liu W, Sun G, Chen Y, Bai L, Zhang Y, He X, Luo Y, Wang Z, Liu Y, Yao Q, Li Y, Qin S, Hu X, Bi F, Zheng R, Ouyang X. CMAB009 plus irinotecan versus irinotecan-only as second-line treatment after fluoropyrimidine and oxaliplatin failure in KRAS wild-type metastatic colorectal cancer patients: promising findings from a prospective, open-label, randomized, phase III trial. Cancer Commun (Lond). 2019 May 24;39(1):28. doi: 10.1186/s40880-019-0374-8.
Results Reference
derived
Learn more about this trial
Study of CMAB009 to Treat KRAS Wild Type Metastatic Colorectal Cancer
We'll reach out to this number within 24 hrs