Safety and Pharmacokinetics of Recombinant Anti-EGFr Antibody in Patients With Metastatic Colorectal Cancer

NCT03017807 | Unknown Phase 1

• 1 other identifier: KL140-I-01-CTP
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

A single-central,open-label,safety,pharmacokinetics,phase I study. Biological:Recombinant Anti-EGFr Antibody Two dose levels: Low-dose level patients received initial dose 100 mg/m2 and 4 weeks later 250 mg/m2 weekly maintenance to the disease progression or unacceptable toxicity or death or withdraw informed consent.High-dose level patients received cetuximab initial dose 400 mg/m2 and 4 weeks later loading 400 mg/m2 and 250 mg/m2 weekly maintenance to the disease progression or unacceptable toxicity or death or withdraw informed consent.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Number of patients with dose limiting toxicity.

  Dose limiting toxicity (DLT) was defined as: grade 4 or 3-time grade 3 cutaneous toxicity,successive 3-time infusion suspension due to grade 3 cutaneous toxicity,any other ≥grade 3 adverse reaction or acute pneumonia, interstitial pneumonia, and other lung diseases.

  4 weeks after the single dose

Secondary Outcomes (2)

• Change from baseline in serum antibody and its neutralizing ability

  Prior to the single dose on day 1 and on the 1st day of 1、2、4、6、9 week after the first administration until 1 month after the last administration.

• Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of anti-EGFR antibody after single dose and under the stable blood concentration.

  4 weeks after the single dose and 1 week under the stable blood concentration after weekly administration.

Study Arms (1)

Recombinant Anti-EGFr Antibody

EXPERIMENTAL

Low-dose level patients received cetuximab initial dose 100 mg/m2 and 4 weeks later 250 mg/m2 weekly maintenance.High-dose level patients received cetuximab initial dose 400 mg/m2 and 4 weeks later loading 400 mg/m2 and 250 mg/m2 weekly maintenance.

Biological: Recombinant Anti-EGFr Antibody

Interventions

Recombinant Anti-EGFr Antibody BIOLOGICAL

Low-dose level patients received cetuximab initial dose 100 mg/m2 and 4 weeks later 250 mg/m2 weekly maintenance to the disease progression or unacceptable toxicity or death or withdraw informed consent.High-dose level patients received cetuximab initial dose 400 mg/m2 and 4 weeks later loading 400 mg/m2 and 250 mg/m2 weekly maintenance to the disease progression or unacceptable toxicity or death or withdraw informed consent.

Recombinant Anti-EGFr Antibody

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages eligible for study between 18 Years and 75 Years.
• Confirmed histological diagnosis of colorectal cancer.
• Subjects with advanced/metastatic Colorectal Cancer(CRC) who have failed to the irinotecan- ,oxaliplatin- and fluoropyrimidine-based regimens or been intolerant to irinotecan or rejected the chemotherapy.
• Eastern Cooperative Oncology Group (ECOG) of 0 or 1.
• Subjects must have a life expectancy of at least 12 weeks.
• Patients with at least one evaluable lesion (evaluable disease) by the RECIST criteria.
• Adequate renal function (creatinine ≤ 1.5 x UNL), liver function (total bilirubin ≤ 1.5 x UNL, alanine aminotransferase(ALT)\< 2.5 x UNL, aspartate aminotransferase(AST) \< 2.5 x UNL or ≤ 5 x UNL if hepatic metastasis) and leucocytes ≥ 3×10\^9, absolute neutrophil count ≥ 1.5×10\^9/L, platelets \> 80×10\^9/L, haemoglobin ≥ 9 g/dl. Electrolyte: in the normal range, or abnormal but no clinical significance (judged by the researchers), allow to give supplements to correct the electrolyte.
• Both women of child-bearing potential and sexually active men must agree to use adequate contraception prior to study entry and for the duration of study participation and for 90 days after the conclusion of study therapy.
• Patients who have capable to understand the procedure and methods of the study,are willing to strictly follow the protocol and sign the the informed consent.

You may not qualify if:

• Previous therapy with anti-EGFR drugs.
• Patients who are receiving other accompanying antineoplastic therapy (including antitumor treatment with traditional Chinese medicine), long-term systemic immune therapy, or hormone therapy except for physiological replacement therapy (for example, people with thyroid hypofunction receive the thyroid hormone).
• Radiotherapy or surgery (except always diagnostic biopsy).
• Patients with known cerebral metastasis or leptomeningeal metastasis.
• Any other malignant tumour in the last five years, except for suitably treated in situ cervical carcinoma or basal cell carcinoma.
• Clinically significant cardiovascular disease, such as heart failure (NYHA Ⅲ-Ⅳ), uncontrolled coronary heart disease, cardiomyopathy, cardiac arrhythmias, hypertension (\> 140/90 mmHg), myocardial infarction in the last half year, echocardiogram showed ejection fraction \< 50%.
• Patients with any symptom of acute or subacute bowel obstruction and/or inflammatory bowel disease.
• Patients with known active and severe infections(\> grade 2, National Cancer Institute Common Toxicity Criteria(NCI-CTC) adverse effect(AE) V. 4.03), including active tuberculosis(TB).
• HIV infection or active hepatitis B or hepatitis C.
• Uncontrolled diabetes (\> grade 2, NCI-CTC AE V. 4.03), severe lung disease (acute lung disease, pulmonary fibrosis that affect the lung function, and interstitial lung disease), liver failure.
• Patients with blood coagulation dysfunction as following situation: prothrombin time (PT) ≥ 1.5 x UNL, thrombin time (TT) ≥ 1.5 x UNL, the part activated clotting time (APTT) ≥ 1.5 x UNL.
• Patients who have blood transfusion, or use the g-csf cytokines etc in the last 10 days.
• Known hypersensitivity to any component of pretreated product.
• Pregnancy or breastfeeding.
• Patients with known drug and/or alcohol abuse.

Sponsors & Collaborators

• Sichuan Kelun Pharmaceutical Co., Ltd: lead
• 307 Hospital of PLA: collaborator

Study Sites (1)

Sichuan Kelun Pharmaceutical Co., Ltd.

Chengdu, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

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

Central Study Contacts

Zhou Jianglin

CONTACT

86-028-67252675; zhoujl@kelun.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2016
• First Posted: January 11, 2017
• Study Start: December 1, 2016
• Primary Completion: June 1, 2017
• Study Completion: October 1, 2017
• Last Updated: January 11, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)