Study of CMAB009 to Treat KRAS Wild Type Metastatic Colorectal Cancer (CRC009)

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

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

Study Overview

• Status: Completed
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: CMAB009 plus Irinotecan; Drug: Irinotecan-only and sequential-CMAB009

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.

• Study Type: Interventional
• Enrollment (Actual): 512
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CMAB009 plus Irinotecan	Drug: CMAB009 plus Irinotecan; Combined with irinotecan 180 mg/m2 every 2 weeks, CMAB009 400 mg/m2 day 1 followed by 250 mg/m2 weekly till disease progression; Other Names: YiMaiLin for irinotecan
Active Comparator: Irinotecan-only and sequential-CMAB009	Drug: Irinotecan-only and sequential-CMAB009; 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.; Other Names: YiMaiLin for irinotecan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	Tumor response was evaluated every 6 weeks and confirmed at least 4 weeks later	Time to progression, assessed up to two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Time to progression, assessed up to two years

Collaborators and Investigators

• Sponsor: Shanghai Zhangjiang Biotechnology Limited Company
• Collaborators: Shanghai Biomabs Pharmaceutical Co., Ltd.
• Investigators: Study Chair: Yuankai Shi, M.D., Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Principal Investigator: B C Mei, Peking Union Medical College Hospital; Principal Investigator: B Li, Chinese PLA Affiliated Central Hospital; Principal Investigator: X J Ming, Affiliated Hospital of Chinese PLA Military Academy of Medical Science; Principal Investigator: B Yi, Tianjin Medical University affiliated Cancer Hospital; Principal Investigator: Y Qiang, NanKai University Affiliated Hospital; Principal Investigator: L Wei, HeBei Medical University Fouth Hospital; Principal Investigator: L Y Peng, Chinese Medical University First Affiliated Hospital; Principal Investigator: W B Cheng, Jinan Military Central Hospital; Principal Investigator: W Z Hai, Shandong Provincal Cancer Hospital; Principal Investigator: Y S Ying, Tongji Medical College of Huazhong University of Science and Technology; Principal Investigator: L Yi, Hunan Provincal Cancer Hospital; Principal Investigator: C Y Gui, Fujian Provincal Cancer Hospital; Principal Investigator: W L Wei, Shanghai Jiaotong University Affiliated First People's Hospital; Principal Investigator: Z Jun, Shanghai Jiaotong University Affiliated Ruijin Hospital; Principal Investigator: H C Hong, Central South University; Principal Investigator: OY Xuenong, Fuzhou Central Hospital of Nanjing Military Command; Principal Investigator: L Jin, Fudan University Affiliated Cancer Hospital; Principal Investigator: Z Y Ping, Zhejiang Provincal Cancer Hospital; Principal Investigator: H X Hua, Guangxi Medical University Affiliated Cancer Hospital; Principal Investigator: L R Cheng, Nanfang Medical University Affiliated Nanfang Hospital; Principal Investigator: L Y Hong, Zhongshan University Affliated Cancer Hospital; Principal Investigator: T Min, Suzhou University Affiliated First Hospital; Principal Investigator: Z Z Xiang, Suzhou University Affiliated Second Hospital; Principal Investigator: C Ying, Jilin Provincal Cancer Hospital; Principal Investigator: F J Feng, Jiangsu Provincal Cancer Hospital; Principal Investigator: Q S Qui, Chinese PLA Affiliated 81 Hospital; Principal Investigator: J Bin, Shanghai Jiaotong University Affiliated Third People's Hospital; Principal Investigator: Z R Sheng, First Affiliated Hospital Bengbu Medical College; Principal Investigator: M G Xin, Nantong Medical College Affiliated Hospital; Principal Investigator: S G Ping, Anhui Medical University Affiliated First Hospital; Principal Investigator: D W Chao, The Fourth Military University Affiliated First Hospital; Principal Investigator: L H Jie, The Third Military University Affiliated First Hospital; Principal Investigator: X Ying, Chongqing University Cancer Hospital; Principal Investigator: F Min, Chongqing First People's Hospital; Principal Investigator: B Feng, Sichuan University Huaxi Hospital; Principal Investigator: W D Lin, Sichuan Provincal People's Hospital; Principal Investigator: Z W Hua, Gansu Provincal Cancer Hospital; Principal Investigator: C Hong, Kunming Central Hospital of Chengdu Military Command

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2009
• Primary Completion (Actual): December 23, 2012
• Study Completion (Actual): July 23, 2015

Study Registration Dates

• First Submitted: March 7, 2012
• First Submitted That Met QC Criteria: March 7, 2012
• First Posted (Estimate): March 9, 2012

Study Record Updates

• Last Update Posted (Actual): April 10, 2019
• Last Update Submitted That Met QC Criteria: April 8, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Metastatic Colorectal Cancer; Phase II/III; KRAS wild-type; CMAB009 Plus Irinotecan
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: CMAB009mCRCⅡ/Ⅲ; CMAB009 (Registry Identifier: 2007L02499)