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

NCT03511963 | Completed Phase 3

• 1 other identifier: HLX04 mCRC03
• Study Type: interventional
• Target: 677
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Colorectal Cancer (mCRC)

Outcome Measures

Primary Outcomes (1)

• PFSR9m

  Progression free survival rate (PFS rate) at Month 9 (PFSR9m)

  0 to 36 weeks

Secondary Outcomes (6)

• BORR

  0 to 48 weeks

• ORR

  6 to 48 weeks

• OSR

  0 to 48 weeks

• TTR

  0-48 weeks

• DOR

  0-48 weeks

Other Outcomes (2)

• Cmax

  0 to 54 weeks

• Ctrough

  0 to 54 weeks

Study Arms (2)

HLX04

EXPERIMENTAL

Drug: HLX04 100 mg in 4 ml Injection

Bevacizumab

ACTIVE COMPARATOR

Drug: Avastin 100 mg in 4 ml Injection

Interventions

HLX04 100 mg in 4 ml Injection DRUG

7.5 mg/kg iv (XELOX+HLX04) 5 mg/kg iv (mFOLFOX6 + HLX04)

HLX04

Avastin 100 mg in 4 ml Injection DRUG

7.5 mg/kg iv (XELOX+HLX04) 5 mg/kg iv (mFOLFOX6 + HLX04)

Bevacizumab

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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).

Sponsors & Collaborators

• Shanghai Henlius Biotech: lead

Study Sites (1)

Nanjing Bayi Hospital Ethics Committee

Nanjing, Jiangsu, 210002, China

Location

Related Publications (2)

• 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.

  PMID: 34086067 DERIVED

• 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.

  PMID: 34014555 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Injections; Bevacizumab

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)

Drug Administration Routes; Drug Therapy; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2018
• First Posted: April 30, 2018
• Study Start: April 9, 2018
• Primary Completion: April 15, 2020
• Study Completion: April 20, 2023
• Last Updated: December 31, 2024

Record last verified: 2024-12

Locations

CN (1)