Safety, Tolerability and Pharmacokinetics of Recombinant Anti-epidermal Growth Factor Receptor(EGFR) Monoclonal Antibody in Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine whether SCT200 is safe and tolerant in the treatment of metastatic colorectal cancer

Official Title
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A Phase I Dose Escalation Study of the Safety, Tolerability and Pharmacokinetics of SCT200, a Recombinant Full Human Anti-epidermal Growth Factor Receptor(EGFR) Monoclonal Antibody，in Patients With Metastatic Colorectal Cancer Following Fluoropyrimidine, Irinotecan and Oxaliplatine Chemotherapy Regiment

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Biological: Recombinant full human Anti-EGFR Monoclonal Antibody


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged from 18 to 70 years; having histologically confirmed metastatic colorectal cancer; having experienced previous treatment failures including fluoropyrimidine, irinotecan and oxaliplatine chemotherapy regiment; having determined wild-type KRAS tumor; having to have measurable or nonmeasurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1; Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; and expected survival of at least ≥3 months; adequate hematological, renal and liver functions: Hematological function: white blood cell count of >4.0×109/L; absolute neutrophil count of >1.5×109/ L; platelet count of >100×109/L; hemoglobin level of >90.0 g/L; Renal function: serum creatinine level of<1.5×upper limit of normal (ULN); Liver function: total bilirubin level of<1.5×ULN; aspartate amino transferase (AST) and alanine amino transferase (ALT) levels of <1.5×ULN; or <5 × ULN for patients with liver metastases; no other malignancies only if they had following malignancies , which were not required to treat or who had curative resection: cervical carcinoma in situ, the skin basal carcinoma or squamous cell carcinoma, bladder epithelial tumors, or only they had some malignancies requirement only surgical therapy and disease free survival≥5 years; no serious nonmalignant diseases including hypertension, diabetes mellitus, coronary artery disease, and mental disorder. not pregnant; or not lactating; or accepted birth control methods during the study; signed an informed consent form which was approved by the institutional review board of the respective medical center . Exclusion Criteria: had received EGFR target treatment including EGFR tyrosine kinase inhibitors(TKI), or anti- EGFR monoclonal antibody; having to be at least 4 weeks beyond prior anticancer therapy (including corticosteroid , or nitrosourea or mitomycin within 6 weeks of study entry) or participating in other clinical trial, or have not recovered from significant toxicities of prior therapy; chronic use of medication that could interfere with the assessment of drug-related toxicities or immunologic activity (high dose prednisone or high dose non-steroid anti-inflammatory medication); had recent major surgery (within 28 days); with symptomatically brain metastases (with the exception of clinically brain metastases stable and of no requirement further treatment); with active infection requirement systemic antibiotics treatment; or serious cardiovascular disease;or with evidence of active hepatitis B or C infection; or with human immunodeficiency virus infection; had acute pulmonary disorder; or interstitial pneumonia; or symptomatically chronic obstructive pulmonary disease (COPD) or with risk factors to COPD; with eye inflammation or infection, or any risk factors who could lead to eye disease; with a history of allergic reaction or protein product allergy including antibodies product; pregnant, or lactating, or not accepted birth control methods including male patients. had a history of alcohol or drugs addiction, or with any risk which may affect the patient's health evaluation or mantle state

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: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm<br>Two phase study of Recombinant full human Anti-epidermal growth factor receptor(EGFR) Monoclonal Antibody: First phase: seven escalating single-dose groups : 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0 mg/kg Second phase: multiple-dose groups 0.5, 1.0, 2.0, 3.0 mg/kg: weekly once for 4 doses; 5.0, 6.0 mg/kg: every two weeks for 2 doses; 4.0 mg/kg: weekly or every two weeks depends on the results of previous dose groups. | Biological: Recombinant full human Anti-EGFR Monoclonal Antibody<br> <br> * Other names: SCT200;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with SCT200-related adverse events |  | up to 105 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the plasma concentration versus time curve (AUC) of SCT200 |  | prior to the initial dose and 0,0.5,1,2,4,8,24,48 hours,4,7,14,21days post- first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Full human anti-EGFR monoclonal antibody (SCT200) ;, metastatic colorectal cancer （mCRC）;, Escalating doses ;, single dose and multiple doses;, safety, tolerability and pharmacokinetics.