Metastatic Colorectal Cancer
Conditions
Keywords
KRAS wild-type, Metastatic Colorectal Cancer, CMAB009 Plus Irinotecan, Phase II/III
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.
Interventions
DRUGCMAB009 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
DRUGIrinotecan-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.
Sponsors
Shanghai Biomabs Pharmaceutical Co., Ltd.
Shanghai Zhangjiang Biotechnology Limited Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate | Time to progression, assessed up to two years | Tumor response was evaluated every 6 weeks and confirmed at least 4 weeks later |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Time to progression, assessed up to two years | 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 |
Outcome results
None listed