Study of CMAB009 to Treat KRAS Wild Type Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: CMAB009 plus Irinotecan
* Drug: Irinotecan-only and sequential-CMAB009


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KRAS wild-type, Metastatic Colorectal Cancer, CMAB009 Plus Irinotecan, Phase II/III