- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03511963
A Clinical Study to Compare the Efficacy, Safety and Immunogenicity of HLX04 and Bevacizumab Combined XELOX or mFOLFOX6 in the First-line Treatment of mCRC
May 6, 2022 updated by: Shanghai Henlius Biotech
A Randomized, Double-blind, Parallel Control, Multicenter, Phase III Clinical Study to Compare the Efficacy and to Evaluate the Safety and Immunogenicity of HLX04 and Bevacizumab Combined With Oxaliplatin and Fluoropyrimidine-based Chemotherapy (XELOX or mFOLFOX6) in the First-line Treatment of Metastatic Colorectal Cancer (mCRC)
This trial is conducted in patients with the recurrent lesion(s) post-surgery or the untreated mCRC.
After stratification with respect to ECOG PS score, chemo regimen, primary tumor location and KRAS and BRAF genotype (complete wild-type/primal type), eligible patients are randomized into two arms at 1:1 ratio to receive HLX04 (Arm A) or Bevacizumab (Arm B) in combination with one of the protocol-defined chemotherapies, modified FOLFOX6 (mFOLFOX6) or XELOX for mCRC until disease progression (PD) or unacceptable toxicity or achieving an operable contingency, whichever occurs first.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
677
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Jiangsu
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Nanjing, Jiangsu, China, 210002
- Nanjing Bayi Hospital Ethics Committee
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Age 18-75 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Life expectancy ≥ 6 months
- Histologically confirmed colorectal cancer with a metastatic / recurrent lesion that cannot be cured by surgery.
- At least one measurable lesion have been the confirmatory detection within 4 weeks prior to the randomization with respect to RECIST 1.1
- No prior first-line systemic anti-tumor therapy for mCRC (including systemic chemotherapy, molecular targeted therapy, biotherapy, and other study treatment) have been identified
- At least 6 months have elapsed if considering the interval from the time of firstly documented metastasis to the post-operational adjuvant chemotherapy termination
Adequate organ function as indicated by the following laboratory values:
- Absolute neutrophil count (ANC) ≥1,500 /mm3(1.5×109 /L)
- Platelets ≥80,000 / mm3(80×109 /L)
- Hemoglobin ≥9 g/dL, within the 2 weeks prior to the screening no need for the transfusion
- Serum creatinine ≤1.5 X upper limit of the normal (ULN) or creatinine clearance ≥ 50 mL/min according to Cockcroft-Gault formula
- Serum total bilirubin ≤ 1.5 X ULN
- AST (SGOT), ALT (SGPT) and alkaline phosphatase (ALK) ≤ 3 X ULN (AST/ALT ≤ 5 X ULN if liver metastatic; ALK ≤ 5 × ULN if liver and/or bone metastastic)
- International Normalized Ratio (INR) or Prothrombin Time (PT) or Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 X ULN; ( if patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intent using goal of anticoagulants)
- The subjects are accredited with good compliance, signed the informed consent, and capable to cooperate, completing the relevant examination and follow-ups.
Exclusion Criteria:
- Targeted medicine(including Bevacizumab, cetuximab, panedol, arbicip, rigofeni, etc) was used before as adjuvant therapy.
- Cerebral and/or leptomeningeal metastasis.
- Bleeding predisposition, high bleeding risk or coagulant disorder, thrombotic event(s) occurrence ≤6 months and/or hemoptysis ≤3 months (≥ 1/2 teaspoons fresh blood each) prior to the screening; use of full dose oral or parenteral anticoagulant or thrombolytic medication (allowing preventative anticoagulation); use of aspirin (> 325 mg/day) or other platelet-inhibition non-steroidal anti-inflammatory drugs within 10 days since the screening; CT/MRI imaging evidence, testimony of the main arteries/veins (such as pulmonary artery or superior vena cava) being infringed, encroached.
- Subjects with uncontrolled hypertension and with a medical history of hypertensive crisis or hypertensive encephalopathy; serious cardiovascular and cerebrovascular diseases, including cerebrovascular accident (CVA) ≤6 months before the screening, transient ischemic attack (TIA), myocardial infarction and significant vascular disease (including but not limited to aortic aneurysms with need for surgical repair or recent evidence of arterial thrombosis), unstable angina, heart failure and serious arrhythmias that are uncontrolled by drugs (New York Heart Association Class ≥2).
- Subjects with non-healing wounds, active peptic ulcer or fracture and active infection; tracheal esophageal fistula, gastrointestinal perforation or gastrointestinal fistula and abdominal abscess in the 6 months prior to the screening;Uncontrolled infection,including HIV,HBV,HCV and syphilis .
- Subjects allergic to bevacizumab, oxaliplatin, 5-FU/capecitabine or folinic acid injection and the relevant ingredients and excipients.
- Pregnant women and lactating women; women of potential childbearing age and male subjects do not use effective contraception during the study period, and during the 6 months after the last study drug administration effective contraception cannot be assured.
- Presence of other active malignancies or a history of other malignancies within the past 5 years, except for carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent.
- Subject is currently enrolled in, or ≤4 weeks since subject participating another investigational device or drug study(s), or subject is receiving other investigational agent(s).
- Any other medical condition that renders disqualification for the inclusion in the study according to the investigator discretionary judgment.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: HLX04
|
7.5 mg/kg iv (XELOX+HLX04) 5 mg/kg iv (mFOLFOX6 + HLX04)
|
Active Comparator: Bevacizumab
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7.5 mg/kg iv (XELOX+HLX04) 5 mg/kg iv (mFOLFOX6 + HLX04)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
PFSR9m
Time Frame: 0 to 36 weeks
|
Progression free survival rate (PFS rate) at Month 9 (PFSR9m)
|
0 to 36 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
BORR
Time Frame: 0 to 48 weeks
|
Best objective response rate (BORR) up to Week 48
|
0 to 48 weeks
|
ORR
Time Frame: 6 to 48 weeks
|
Objective response rate (ORR) at Weeks 6, 12, 18, 24, 36,42,48
|
6 to 48 weeks
|
OSR
Time Frame: 0 to 48 weeks
|
Overal survival rate: the time from the date of randomization to the date of documented clinical or radiological progression or death due to any cause within 48 weeks after first visit
|
0 to 48 weeks
|
TTR
Time Frame: 0-48 weeks
|
Time to response (TTR)
|
0-48 weeks
|
DOR
Time Frame: 0-48 weeks
|
Duration of response (DOR)
|
0-48 weeks
|
SAE
Time Frame: 0-48 weeks
|
incidence of serious adverse events (SAE)
|
0-48 weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cmax
Time Frame: 0 to 54 weeks
|
Cmax following first dose and the dose of Week 18;
|
0 to 54 weeks
|
Ctrough
Time Frame: 0 to 54 weeks
|
Ctrough before the first dose of Cycle2, Week 18, Week 36;
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0 to 54 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Zhu X, Qian H, Sun J, Wu M, Yu C, Ding Y, Zhang X, Chai K, Li X. A phase 1 randomized study compare the pharmacokinetics, safety and immunogenicity of HLX04 to reference bevacizumab sourced from the United States, the European Union, and China in healthy Chinese male volunteers. Cancer Chemother Pharmacol. 2021 Sep;88(3):465-474. doi: 10.1007/s00280-021-04297-z. Epub 2021 Jun 4.
- Qin S, Li J, Bai Y, Shu Y, Li W, Yin X, Cheng Y, Sun G, Deng Y, Zhong H, Li Y, Qian X, Zhang L, Zhang J, Chen K, Kang W; HLX04-mCRC03 Investigators. Efficacy, Safety, and Immunogenicity of HLX04 Versus Reference Bevacizumab in Combination with XELOX or mFOLFOX6 as First-Line Treatment for Metastatic Colorectal Cancer: Results of a Randomized, Double-Blind Phase III Study. BioDrugs. 2021 Jul;35(4):445-458. doi: 10.1007/s40259-021-00484-9. Epub 2021 May 20.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 9, 2018
Primary Completion (Actual)
April 15, 2020
Study Completion (Anticipated)
April 30, 2024
Study Registration Dates
First Submitted
March 21, 2018
First Submitted That Met QC Criteria
April 27, 2018
First Posted (Actual)
April 30, 2018
Study Record Updates
Last Update Posted (Actual)
May 11, 2022
Last Update Submitted That Met QC Criteria
May 6, 2022
Last Verified
May 1, 2022
More Information
Terms related to this study
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
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Bevacizumab
Other Study ID Numbers
- HLX04 mCRC03
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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