Clinical trial NCT03405272: Safety and Efficacy of Recombinant Anti-EGFR Monoclonal Antibody in Patients With Wild-type RAS and BRAF mCRC
Official title: Recombinant Anti-EGFR Monoclonal Antibody（SCT200） in Patients With Chemotherapy- Refractory Wild Type RAS and BRAF Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Full human anti-EGFR monoclonal antibody (SCT200)
metastatic colorectal cancer （mCRC）
Lead sponsor: Sinocelltech Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
First posted: 2018-01-23
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Treated with recombinant anti-EGFR Monoclonal antibody（SCT200）until disease progression
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of recombinant anti-EGFR Monoclonal antibody（SCT200）in patients with wild-type RAS and BRAF mCRC treated with fluorouracil, oxaliplatin and irinotecan after failure of standard therapy


Eligibility criteria: Inclusion Criteria:

1. Able to provide written informed consent and can understand and comply with the requirements of the study;
2. Men and women ≥ 18 years of age;
3. Life expectancy of longer than 3 months ( clinical assessment);
4. With an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1;
5. Have been diagnosed as mCRC verified histologically;
6. Patients treated with fluorouracil, oxaliplatin and irinotecan after failure of standard therapy. Disease progressed or developed non-tolerable toxicity after systemic chemotherapy：a. at least one treatment cycle should be completed, and maintenance therapy using one of the doublets is considered as the same line of therapy ; b. May have received adjuvant therapy for primary colorectal cancer provided that at least 6 months have elapsed from the time the adjuvant therapy was concluded and recurrent disease was documented;
7. RAS and BRAF wildtype status of primary colorectal cancer or related metastasis;
8. 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 2.5 times IULN, or less than/equal to 5 times IULN if known liver metastases; Total bilirubin less than/equal to 1.5 within institutional upper limit of normal (IULN); Serum creatinine less than/equal to 1.5 times IULN; Electrolyte: magnesium greater than/equal to normal.
9. According to RECIST 1.1 , patients must have at least one measurable lesion that can be accurately assessed at baseline and is suitable for repeated assessment by CT, MRI. Longest diameter greater than/equal to10mm（CT scan slice thickness no greater than 5 mm）, a lymph node must be ≥15mm in short axis when assessed by CT scan.

Exclusion Criteria:

1. Patient with active brain metastasis or indicated for symptomatic treatment for brain metastasis, untreated with proper radiation therapy, showing clinical symptoms or symptom stable time less than 28 days;
2. Patients with other primary malignancies within the past 5 years except non-melanoma skin cancer, carcinoma in situ of cervix or prostatic intraepithelial neoplasia;
3. Patients who are allergic to analogue of SCT200 and/or its inactive ingredients;
4. Patients administrated EGFR target treatment including EGFR TKI agent or anti- EGFR monoclonal antibody;
5. 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);
6. Patients are currently enrolled in other research devices or in research drugs, or less than 4 weeks from other research drugs or devices.
7. Patients received major surgery(such as need general anesthesia ) within 4 weeks , should recover from the injury associated with the surgery.
8. Patients treated with EPO, G-CSF or GM-CSF.
9. Patients who have clinically significant cardiovascular disease (defined as unstable angina pectoris, symptomatic congestive heart failure (NYHA, greater than II), uncontrollable severe arrhythmia);
10. Patients occurred myocardial infarction within 6 months.
11. Patients who have interstitial lung disease, such as interstitial pneumonia, pulmonary fibrosis, or CT or MRI reminder ILD .
12. Patients with clinical symptoms, required clinical intervention or stable time less than 4 weeks of serous cavity effusion (such as pleural effusion and ascites);
13. Patients with serious psychological or psychiatric disorders which may affect subject compliance in this clinical study;
14. Pregnant or lactating women, or women who planned to be pregnant within 6 months of treatment;
15. Patients who were not willing to accept effective contraceptive measures (including male or female subjects) during treatment and within 6 months after treatment;
16. 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);
17. Patients with uncontrolled active infections before enrollment 2 weeks (except simple urinary tract infection or upper respiratory tract infection);
18. Patients have alcohol or drug addiction;
19. Inability to comply with study and/or follow-up procedures

Primary outcomes:
measure: Objective response rate
timeFrame: 1 year
Secondary outcomes:
measure: Objective response rate - left side
timeFrame: 1 year
measure: Best of response
timeFrame: 1 year
measure: Duration of response
timeFrame: 1 year
measure: Disease control rate
timeFrame: 1 year
measure: Time to response
timeFrame: 1 year
measure: Progression free survival
timeFrame: 1 year
measure: Overall survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Cancer hospital Chinese academy of medical sciences
state: Beijing
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital Of Sun Yat-sen University
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital.
state: Henan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Dalian
country: China
facility: The First Affiliated Hospital of Dalian Medical University
state: Liaoning
city: Xi'an
country: China
facility: Xiking Hospital
state: Shaanxi
city: Linyi
country: China
facility: Lin Yi Cancer Hospital
state: Shandong
city: Shanghai
country: China
facility: Zhongshan hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Urumqi
country: China
facility: The First Affiliated Hospital Of Xinjiang Medical University
state: Xinjiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: yuankai shi, MD
role: PRINCIPAL_INVESTIGATOR
References: