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

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

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

Study Overview

• Status: Unknown
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Biological: Recombinant full human Anti-EGFR Monoclonal Antibody

• Study Type: Interventional
• Enrollment (Anticipated): 21
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. 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;
  2. Renal function: serum creatinine level of<1.5×upper limit of normal (ULN);
  3. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single arm; 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; Other Names: SCT200

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Time Frame
Time to Disease Progression (TTP) of SCT200	up to 105 days

Collaborators and Investigators

• Sponsor: Sinocelltech Ltd.

Publications and helpful links

General Publications

• Zhang W, Han X, Yang L, Song Y, Xie L, Gai W, Wang Y, Shi Y. Safety, pharmacokinetics and efficacy of SCT200, an anti-EGFR monoclonal antibody in patients with wild-type KRAS/NRAS/BRAF metastatic colorectal cancer: a phase I dose-escalation and dose-expansion study. BMC Cancer. 2022 Oct 28;22(1):1104. doi: 10.1186/s12885-022-10147-9.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: August 5, 2014
• First Submitted That Met QC Criteria: August 5, 2014
• First Posted (Estimate): August 7, 2014

Study Record Updates

• Last Update Posted (Estimate): April 9, 2015
• Last Update Submitted That Met QC Criteria: April 8, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Full human anti-EGFR monoclonal antibody (SCT200) ;; metastatic colorectal cancer （mCRC）;; Escalating doses ;; single dose and multiple doses;; safety, tolerability and pharmacokinetics.
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: SCT200mCRCI