Safety and Efficacy of SCT200 in Patients With Advanced Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of recombinant anti-EGFR monoclonal antibody（SCT200）in patients with advanced esophageal squamous cell carcinoma progressed following treatment with taxane/platinum/fluorouracil.

Detailed Description
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This is a open label, single-arm multicenter phase Ib study,and is designed to evaluate Objective Response Rate (ORR) in advanced esophageal squamous cell carcinoma progressed following treatment with taxane/platinum/fluorouracil treated with anti-EGFR monoclonal antibody SCT200.

Official Title
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Phase Ib, Open-label, Single-arm, Multicenter Study to Evaluate Safety and Efficacy of SCT200 in Patients With Advanced Esophageal Squamous Cell Carcinoma Progressed Following Treatment With Taxane/Platinum/Fluorouracil

Conditions
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Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: recombinant anti-EGFR monoclonal antibody


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females. Aged 18 to 75 years old; Histologically or cytologically proven squamous cell carcinoma of the esophagus, which is locally unresectable or distant metastatic disease; Disease progressed following standard therapies. Patients has treated with taxane/platinum/fluorouracil and/or radiotherapy. Failure of standard therapy ：Disease progressed or developed non-tolerable toxicity during or within 3 months after last systemic chemotherapy or radical concurrent chemoradiotherapy. For adjuvant therapy/neoadjuvant therapy, disease relapse or progression during treatment or within 6 months after treatment is considered as failure of standard therapy; According to RECIST 1.1 , patients must have at least one measurable lesion which was not treated with local treatment such as radiotherapy. Tumour lesions situated in a previously irradiated area which have been demonstrated progression in the lesion, are considered measurable; With an Eastern Cooperative Oncology Group (ECOG) performance status 0-1; Life expectancy of longer than 3 months ( clinical assessment); Adequate organ and marrow function as defined below: Absolute neutrophil count (ANC) greater than/equal to 1.5×l09/L; Platelets greater than/equal to 75×109/L; Hemoglobin greater than/equal to 80g/L; Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than/equal to 3 times ULN, or less than/equal to 5 times ULN if known liver metastases; Total bilirubin less than/equal to 1.5 within institutional limit of normal (ULN); Serum creatinine less than/equal to 1.5 times ULN; Electrolyte: magnesium greater than/equal to normal. Women of childbearing potential must not be pregnant as assessed by a negative urine or serum beta HCG test upon admission to the hospital, and must agree to use adequate contraception during the study until to 6 months after the last dose of SCT200.For male,if his sexual partners is child-bearing potential, he should use effective contraception from the time of signing the informed consent form until at least 6 months after the last dose of study drug. Able to provide written informed consent and can understand and comply with the requirements of the study; Exclusion Criteria: Patients with active central nervous system metastasis or a history of central nervous system metastasis;(If the subject has been suspected with central nervous system metastasis,imaging examination confirmation must be performed within 28 days to exclude central nervous system metastasis; Patients with other primary malignancies except cured of non-melanoma skin cancer, carcinoma in situ of cervix or prostatic intraepithelial neoplasia; Patients who are allergic to analogue of SCT200 and/or its inactive ingredients; Patients administrated EGFR target treatment including EGFR TKI agent or anti- EGFR monoclonal antibody; Within 4 weeks, patients received anti-tumor drugs (such as chemotherapy, hormone therapy, immune therapy, the antibody therapy, radiotherapy) or research drugs, or patients with grade 2 or more adverse reaction caused by previous anti-tumor therapy(except alopecia or neurotoxicity grade 2 or less); Patients are currently enrolled in other research devices or in research drugs, or less than 4 weeks from other research drugs or devices; Patients received major surgery(such as need general anesthesia ) within 4 weeks , should recover from the injury associated with the surgery; Patients treated with EPO, G-CSF or GM-CSF; Patients who have clinically significant cardiovascular disease (defined as unstable angina pectoris, symptomatic congestive heart failure (NYHA, greater than II), uncontrollable severe arrhythmia); Patients occurred myocardial infarction within 6 months; Patients who have interstitial lung disease, such as interstitial pneumonia, pulmonary fibrosis, or CT or MRI reminder ILD ; Patients with clinical symptoms, required clinical intervention or stable time less than 4 weeks of serous cavity effusion (such as pleural effusion and ascites); Patients with active hepatitis B or active hepatitis C, etc. (for patients with a history of hepatitis B, whether treated or not, HBV DNA ≥104 or ≥ 2000IU/ml, HCV RNA≥15IU/ml); HIV antibody positive (if there is no clinical evidence suggesting that there may be HIV infection, there is no need to detect); Patients with uncontrolled active infections before enrollment 2 weeks (except simple urinary tract infection or upper respiratory tract infection); Patients have alcohol or drug addiction; Patients with serious abnormal medical, psychological or laboratory results history which may affect explanation of study results; Subjects are considered not suitable for the study by investigator,who have other conditions that may affect their adherence and the evaluation of study indicators.,

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: recombinant anti-EGFR monoclonal antibody（SCT200）<br>6.0mg/kg QW for 6 weeks, then 8.0mg/kg Q2W | Drug: recombinant anti-EGFR monoclonal antibody<br>* Experimental: Recombinant Anti-EGFR Monoclonal Antibody（SCT200）. Initially, SCT200 6.0mg/kg will be administered at day 1 every week for a maximum of 6 cycles. After 6 cycles SCT200 8.0mg/kg will be administered at day 2 every weeks until disease progression.<br>* Other names: SCT200;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | ORR is defined as proportion of patients achieving complete response (CR) or partial response (PR) according to RECIST v1.1 during trial treatment. | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AEs) | AE are assessed according to NCI CTCAE v4.03. | one year | 
| PFS | PFS is defined as the time from first dose of SCT200 until the date of first documentation of progression or date of death, whichever occurs first,according to RECIST v1.1 criteria. | one year | 
| Duration of response (DOR) | DOR is defined as time from the date when a patient first meets the criteria for CR or PR according to RECIST v1.1, until the date that progressive disease (PD) is objectively documented or death, whichever occurs first | one year | 
| Overall survival (OS) | OS is defined as time from first dose of SCT200 until the date of death from any cause. | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carcinoma, Carcinoma, Squamous Cell, Esophageal Neoplasms, Neoplasms, Squamous Cell, Esophageal Diseases, Epidermal growth factor receptor, EGFR, SCT200