Open Label Randomized Bioequivalence Study to Evaluate the Pharmacokinetic and Safety Profile of Bevacizumab Biosimilar (BEVZ92) vs Bevacizumab (AVASTIN®), Both With FOLFOX or FOLFIRI, in First-line Treatment for mCRC Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 142
- 试验地点
- 18
- 主要终点
- AUC at Steady State (AUCss) of BEVZ92 and Avastin®
研究概览
简要总结
This is a multicenter, open label, randomized bioequivalence study of BEVZ92 (bevacizumab biosimilar) and Avastin® with 2 parallel arms to compare the pharmacokinetic (PK) profile of BEVZ92 and Avastin® in combination with FOLFOX (any) or FOLFIRI chemotherapy.
FOLFOX (any) or FOLFIRI will be chosen as per investigator criteria based on the hospital standard of care.
详细描述
Planned enrolment duration: 12 months. Pre-treatment period (included in enrolment period): 1 month. Treatment period: Patients will continue treatment until disease progression or unacceptable toxicity, or withdrawal of consent.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must not have had prior chemotherapy for advanced or metastatic disease. Patients could have received adjuvant chemotherapy or adjuvant chemo-radiotherapy.
- •Patient with mCRC for whom bio-chemotherapy is indicated.
- •Patients must have at least one measurable non-irradiated site of disease according to RECIST (version 1.1) criteria. If the patient has had previous irradiation of the marker lesion(s), there must be evidence of progression since the radiation.
- •Minimum of 4 weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Adequate bone marrow function
- •Adequate liver function defined within specific parameters
- •Adequate renal function defined within specific parameters
- •Adequate coagulation parameters defined within specific parameters
- •Negative pregnancy test for females of a childbearing potential.
- •Use of an effective form of contraception during the study (for subjects of childbearing potential and their partners).
- •Life expectation ≥ 3 months
排除标准
- •Prior treatment for advanced or metastatic colorectal cancer.
- •Prior treatment with an anti-angiogenesis agent, in either the neoadjuvant or adjuvant setting.
- •Concurrent use of investigational anti-neoplastic agents (including up to 4 weeks prior to enrolment).
- •History of any other malignancy unless the malignancy is in complete remission and the patient has been off all therapy for that malignancy for at least 5 years.
- •Chronic treatment with systemic steroids or other immunosuppressive agents; topical or inhaled corticosteroids are allowed.
- •Scheduled immunization with attenuated live vaccines during study period or within 1 week prior to study entry.
- •Uncontrolled brain or lepto-meningeal metastases, including patients who continue to require glucocorticoids for brain or lepto-meningeal metastases.
- •Patients with active bleeding or history of bleeding diathesis on oral anti-vitamin K medication (except low dose coumadin) within the past 6 month prior to randomization or coagulopathy.
- •Patients with history of cerebral vascular accident, transient ischemic attack, or subarachnoid haemorrhage within the past 6 month prior to randomization.
- •Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
- •Patients with serious non-healing wound, ulcer, bone fracture, or with a major surgical procedure, or significant traumatic injury within 4 weeks prior to randomization
- •Patients with clinical symptoms or signs of gastrointestinal obstruction that require parenteral hydration and/or nutrition.
- •Patients with history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months prior to randomization.
- •Patients with history of hypersensitivity to any of the study drugs or ingredients.
研究组 & 干预措施
Avastin® (bevacizumab, ref. product)
Bevacizumab 25mg/ml (strength: 100mg/4ml)
干预措施: Avastin® (bevacizumab, reference product) (Drug)
Bevacizumab biosimilar (BEVZ92)
Bevacizumab 25 mg/mL (strength: 100 mg/4 mL).
干预措施: Bevacizumab biosimilar (BEVZ92) (Drug)
结局指标
主要结局
AUC at Steady State (AUCss) of BEVZ92 and Avastin®
时间窗: AUCss: 0 to 336 hours after the administration of Cycle 7 infusion (Week 13).
To compare the PK profile of BEVZ92 and Avastin®, both administered in combination with FOLFOX (any) or FOLFIRI, by means of comparing the truncated area under the concentration-versus-time curve calculated over a dosage interval at steady state (i.e. at Cycle 7; AUCss). For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% CI of the ratio of a log-transformed exposure measure (AUC) falls completely within the range 80-125%.
Area Under the Concentration-versus-time Curve (AUC) at Cycle 1 (AUC0-336h) of BEVZ92 and Avastin®
时间窗: AUC0-336 hrs: 0 to 336 hours after start of the first infusion
To compare the pharmacokinetic (PK) profile of BEVZ92 and Avastin®, both administered in combination with FOLFOX (any) or FOLFIRI, by means of comparing the truncated AUC calculated from start of the first infusion until start of the second infusion (i.e. at Cycle 1; AUC0-336h) For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) of the ratio of a log-transformed exposure measure (AUC) falls completely within the range 80-125%.
次要结局
- Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Reported With BEVZ92 and Avastin®(From first study dose and up to 30 days after the end of study treatment for each patient, for an average of 11 months)
- Cmax,ss of BEVZ92 and Avastin®(Cmax, ss: 0 to 336 hours post-dose after the administration of Cycle 7 infusion (Week 13))
- Anti-Drug Antibody (ADA) of BEVZ92 and Avastin®(At baseline, and on Day 1 (pre-dose) of Cycles: 1, 5 and 8, and 12 months after first drug administration)
- Volume of Distribution (Vd) of BEVZ92 and Avastin®(Vd: 0 to 336 hours after the administration of the Cycle 7 infusion.)
- Objective Response Rate (ORR) of BEVZ92 and Avastin®(Every four weeks. Up to 48 weeks)
- Cmax,sd of BEVZ92 and Avastin®(Cmax, sd: 0 to 336 hours after start of the first infusion.)
- Progression-free Survival (PFS) of BEVZ92 and Avastin®(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 weeks.)
- Ctrough,sd of BEVZ92 and Avastin®(Ctrough, sd: 0 to 336 hours after start of the first infusion.)
- Ctrough,ss of BEVZ92 and Avastin®(Ctrough, ss: 0 to 336 hours after the administration of the Cycle 7 infusion.)
- Elimination Half-life (t1/2) of BEVZ92 and Avastin®(t1/2: 0 to 336 hours after the administration of the Cycle 7 infusion.)
- Elimination Rate Constant (Kel) of BEVZ92 and Avastin®(Kel: 0 to 336 hours after the administration of the Cycle 7 infusion.)