A Preliminary Clinical Study on the Pharmacokinetics and Safety of CDP1 in Patients With Advanced CRC or HNSCC

NCT03491709 | Unknown Phase 1

• 1 other identifier: CDP100001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Colorectal cancer (CRC) is one of the most common human malignant tumors. The incidence and mortality of colorectal cancer in our country are on the rise. Surgery-based, combined with chemotherapy, radiotherapy comprehensive treatment, is the main treatment of colorectal cancer. Surgical resection has been recognized as the primary treatment of colorectal cancer. However, due to the majority of patients already advanced at the time of diagnosis, some difficulties are brought to radical surgery. Therefore, the importance of chemotherapy for colorectal cancer gradually been clinically recognized, But rarely survive more than 18 months." In addition to chemotherapy, there is now a more ideal model of cancer treatment- molecular targeted therapies, including monoclonal antibody drugs such as cetuximab, as well as small molecule tyrosine kinases Inhibitors gefitinib and so on. Molecular targeted drugs make use of the difference in molecular biology between tumor cells and normal cells. Targeting drugs to tumor cells and inhibiting the growth and proliferation of the cells can achieve the therapeutic effect, which has the advantages of high specificity and low adverse reaction. The bio-targeted drug cetuximab is the first drug approved to marketed as an epidermal growth factor receptor (EGFR)-targeting immunoglobulin 1（IgG1）monoclonal antibody. Cetuximab, either monotherapy or combined radiotherapy and chemotherapy, can exert excellent anti-tumor activity in EGFR-positive malignant tumors and can significantly enhance the efficacy of radiotherapy and chemotherapy. Reference to cetuximab injection, guilin sanjin Co., Ltd. and dragonboat Co., Ltd. jointly developed a recombinant anti-EGFR human mouse chimeric monoclonal antibody (R \& D code: CDP1).The primary structure of CDP1 is exactly the same with cetuximab, the higher structure and Physical and chemical properties and cetuximab are highly similar. Pharmacodynamic activity in vivo and in vitro, pharmacokinetic characteristics and toxicological reactions are also similar to cetuximab. CDP1 selected with cetuximab consistent formulations, prescriptions, specifications. CDP1 was approved by China Food and Drug Administration (No. 2016L06884) in August 2016 for clinical studies. According to the contents of the document and guidelines for biological analogs, the clinical pharmacokinetic and clinical effectiveness comparison tests of CDP1 and the safety and immunogenicity assessment are planned.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetic Parameters: Area Under the Serum Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-t) After First Infusion

  Single-dose Phase: Pharmacokinetic parameters: AUC(0-t) for CDP1

  Up to 59 Days

Secondary Outcomes (15)

• Pharmacokinetic parameters: Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-00) After First Infusion

  Up to 59 Days

• Pharmacokinetic parameters: Observed Maximum Serum Concentration (Cmax) of CDP1 After First Infusion

  Up to 59 Days

• Pharmacokinetic parameters: Mean Residence Time of Drug in the Body (MRT) of CDP1 After First Infusion

  Up to 59 Days

• Pharmacokinetic parameters: Apparent Terminal Half-life (t1/2) of CDP1 After First Infusion

  Up to 59 Days

• Pharmacokinetic parameters: Total Body Clearance of Drug From Serum (CL) After First Infusion

  Up to 59 Days

Study Arms (2)

anti-EGFR monoclonal antibody

EXPERIMENTAL

Recombinant anti-EGFR human mouse chimeric monoclonal antibody injection 250mg/m2 single administration

Drug: anti-EGFR monoclonal antibody

Cetuximab injection

ACTIVE COMPARATOR

Cetuximab,Erbitux 250mg/m2 single administration

Drug: Cetuximab injection

Interventions

anti-EGFR monoclonal antibody DRUG

Recombinant anti-EGFR human mouse chimeric monoclonal antibody injection

Also known as: CDP1

anti-EGFR monoclonal antibody

Cetuximab injection DRUG

Cetuximab injection

Also known as: Erbitux

Cetuximab injection

Eligibility Criteria

• Age: 18 Years - 75 Years
• Gender Eligibility Details: Age 18 \~ 75 (inclusive) years , male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 \~ 75 (inclusive) years , male.
• Histologically or cytologically confirmed ras genotype is wild-type patients with advanced metastatic colorectal cancer, at least second-line chemotherapy (including oxaliplatin, irinotecan and fluorouracil drugs) failed, or intolerant to Irinotecan or chemotherapy-denied patients.
• ECOG physical score 0-2 points.
• Expected survival time of 3 months or more.
• According to RECIST 1.1, there is at least one assessable tumor lesion.
• No serious hematological system, liver function, renal function and coagulation dysfunction:Neutrophils ≥1.5 × 109 / L, platelets ≥75 × 109 / L, hemoglobin≥90g / L; total bilirubin≤1.5 times ULN, alanine aminotransferase (ALT)≤2.5 times ULN,aspartate transaminase (AST) ≤2.5 times ULN (liver metastasis ALT ≤ 5 times ULN, AST≤ 5 times ULN);Serum creatinine ≤1.5 times ULN;Activated partial thromboplastin time (APTT) ≤1.5 times ULN, prothrombin time (PT) ≤1.5 times ULN, international normalized ratio (INR) ≤1.5 times ULN.
• Eligible patients with fertility must agree to use reliable methods of contraception (hormonal or barrier abstinence) for at least 12 weeks during and after the last dose of medication.
• Subjects should be informed of the study prior to the test and voluntarily sign a written informed consent form.

You may not qualify if:

• Chemotherapy, biotherapy, radiation therapy, endocrine therapy, small molecule targeted therapies and other anti-tumor, etc. within 4 weeks prior to the start of study drug use or within 5 half-lives of the known drug (whichever is longer) Anti-cancer therapy, or other experimental drug treatment (except nitrosourea, mitomycin C and fluorouracil oral drugs),nitrosourea or mitomycin C for 6 weeks. Fluorouracil-based oral medications, such as tiotropium and capecitabine, have an interval of at least 2 weeks between the last oral dose and study drug use.
• Have previously received anti-EGFR monoclonal antibody treatment.
• EGFR antibody drug-resistant antibody (ADA) positive.
• Within 3 months prior to enrollment, major organ surgery (excluding biopsy) or significant trauma occurred.
• The adverse reactions of previous anti-tumor therapy have not been restored to CTCAE 4.03 grade ≤1 (excluding hair loss).
• Uncontrolled active infections.
• Have a history of immunodeficiency, including HIV antibody test positive.
• Treponema anti-positive.
• Chronic hepatitis B virus (HBV) infection; Hepatitis C virus (HCV) infection.
• Serious history of cardiovascular disease: including ventricular arrhythmias requiring clinical intervention; acute coronary syndromes, congestive heart failure, stroke or other cardiovascular events of grade III and higher within 6 months; New York, USA Heart Association (NYHA. Cardiac function grade ≥II or Left ventricular ejection fraction(LVEF) \<50%; poorly controlled hypertension (systolic blood pressure\> 150 mmHg, diastolic blood pressure\> 90 mmHg).
• Interstitial lung disease.
• There are other serious history of systemic diseases, the researchers judged not suitable for clinical trials of patients.
• Alcohol or drug dependence is known.
• Persons with mental disorders or poor compliance.
• Moderate or severe infusion-related reactions, including anaphylaxis, have been reported in the past when using monoclonal antibody drugs.

Sponsors & Collaborators

• Dragonboat Biopharmaceutical Company Limited: lead
• Shanghai East Hospital: collaborator

Study Sites (1)

Shanghai East Hospital Phase 1 Clinical Trial Center

Shanghai, Shanghai Municipality, 201203, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Li Jin, doctor

  Shanghai East Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2018
• First Posted: April 9, 2018
• Study Start: July 1, 2018
• Primary Completion: September 17, 2019
• Study Completion: December 1, 2019
• Last Updated: October 31, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)