Clinical trial NCT01550055: Study of CMAB009 to Treat KRAS Wild Type Metastatic Colorectal Cancer
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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Metastatic Colorectal Cancer
Keywords: KRAS wild-type
Metastatic Colorectal Cancer
CMAB009 Plus Irinotecan
Phase II/III
Lead sponsor: Shanghai Zhangjiang Biotechnology Limited Company
Sponsor class: INDUSTRY
Collaborators: name: Shanghai Biomabs Pharmaceutical Co., Ltd.
First posted: 2012-03-09
Enrollment: 512
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall response rate
timeFrame: Time to progression, assessed up to two years
Secondary outcomes:
measure: Progression-free Survival
timeFrame: Time to progression, assessed up to two years
Other outcomes:
Locations:
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Yuankai Shi, M.D.
role: STUDY_CHAIR
affiliation: Peking Union Medical College Hospital
name: B C Mei
role: PRINCIPAL_INVESTIGATOR
affiliation: Chinese PLA Affiliated Central Hospital
name: B Li
role: PRINCIPAL_INVESTIGATOR
affiliation: Affiliated Hospital of Chinese PLA Military Academy of Medical Science
name: X J Ming
role: PRINCIPAL_INVESTIGATOR
affiliation: TianJin Medical University Affiliated Cancer Hospital
name: B Yi
role: PRINCIPAL_INVESTIGATOR
affiliation: NanKai University Affiliated Hospital
name: Y Qiang
role: PRINCIPAL_INVESTIGATOR
affiliation: HeBei Medical University Fouth Hospital
name: L Wei
role: PRINCIPAL_INVESTIGATOR
affiliation: Chinese Medical University First Affiliated Hospital
name: L Y Peng
role: PRINCIPAL_INVESTIGATOR
affiliation: Jinan Military Central Hospital
name: W B Cheng
role: PRINCIPAL_INVESTIGATOR
affiliation: Shandong Provincal Cancer Hospital
name: W Z Hai
role: PRINCIPAL_INVESTIGATOR
affiliation: Tongji Medical College of Huazhong University of Science and Technology
name: Y S Ying
role: PRINCIPAL_INVESTIGATOR
affiliation: Hunan Provincal Cancer Hospital
name: L Yi
role: PRINCIPAL_INVESTIGATOR
affiliation: Fujian Provincal Cancer Hospital
name: C Y Gui
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai Jiaotong University Affiliated First People's Hospital
name: W L Wei
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai Jiaotong University Affiliated Ruijin Hospital
name: Z Jun
role: PRINCIPAL_INVESTIGATOR
affiliation: Central South University
name: H C Hong
role: PRINCIPAL_INVESTIGATOR
affiliation: Fuzhou Central Hospital of Nanjing Military Command
name: OY Xuenong
role: PRINCIPAL_INVESTIGATOR
affiliation: Fudan University Affiliated Cancer Hospital
name: L Jin
role: PRINCIPAL_INVESTIGATOR
affiliation: Zhejiang Provincal Cancer Hospital
name: Z Y Ping
role: PRINCIPAL_INVESTIGATOR
affiliation: Guangxi Medical University Affiliated Cancer Hospital
name: H X Hua
role: PRINCIPAL_INVESTIGATOR
affiliation: Nanfang Medical University Affiliated Nanfang Hospital
name: L R Cheng
role: PRINCIPAL_INVESTIGATOR
affiliation: Zhongshan University Affliated Cancer Hospital
name: L Y Hong
role: PRINCIPAL_INVESTIGATOR
affiliation: Suzhou University Affiliated First Hospital
name: T Min
role: PRINCIPAL_INVESTIGATOR
affiliation: Suzhou University Affiliated Second Hospital
name: Z Z Xiang
role: PRINCIPAL_INVESTIGATOR
affiliation: Jilin Provincal Cancer Hospital
name: C Ying
role: PRINCIPAL_INVESTIGATOR
affiliation: Jiangsu Provincal Cancer Hospital
name: F J Feng
role: PRINCIPAL_INVESTIGATOR
affiliation: Chinese PLA Affiliated 81 Hospital
name: Q S Qui
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai Jiaotong University Affiliated Third People's Hospital
name: J Bin
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Bengbu Medical University
name: Z R Sheng
role: PRINCIPAL_INVESTIGATOR
affiliation: Nantong Medical College Affiliated Hospital
name: M G Xin
role: PRINCIPAL_INVESTIGATOR
affiliation: Anhui Medical University Affiliated First Hospital
name: S G Ping
role: PRINCIPAL_INVESTIGATOR
affiliation: The Fourth Military University Affiliated First Hospital
name: D W Chao
role: PRINCIPAL_INVESTIGATOR
affiliation: The Third Military University Affiliated First Hospital
name: L H Jie
role: PRINCIPAL_INVESTIGATOR
affiliation: Chongqing University Cancer Hospital
name: X Ying
role: PRINCIPAL_INVESTIGATOR
affiliation: Chongqing First People's Hospital
name: F Min
role: PRINCIPAL_INVESTIGATOR
affiliation: Sichuan University Huaxi Hospital
name: B Feng
role: PRINCIPAL_INVESTIGATOR
affiliation: Sichuan Provincal People's Hospital
name: W D Lin
role: PRINCIPAL_INVESTIGATOR
affiliation: Gansu Provincal Cancer Hospital
name: Z W Hua
role: PRINCIPAL_INVESTIGATOR
affiliation: Kunming Central Hospital of Chengdu Military Command
name: C Hong
role: PRINCIPAL_INVESTIGATOR
References:
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.