A Phase III Randomized Study Evaluating the Efficacy and Safety of Continued and Re-induced Bevacizumab in Combination With Chemotherapy for Patients With Locally Recurrent or Metastatic Breast Cancer After First-line Chemotherapy and Bevacizumab Treatment
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 494
- 主要终点
- Percentage of Participants Estimated to be Alive and Free of Second-Line Disease Progression at Month 12
研究概览
简要总结
This randomized, open-label, parallel-group study will assess the efficacy and s afety of Avastin (bevacizumab) in combination with chemotherapy versus chemother apy alone as second- and third-line therapy in patients with locally recurrent o r metastatic breast cancer progressing after first-line therapy with Avastin and chemotherapy. Patients will be randomized to receive either Avastin (15 mg/kg e very 3 weeks or 10 mg/kg every 2 weeks intravenously) plus standard chemotherapy or chemotherapy alone. Anticipated time on study treatment is until third-line disease progression or unacceptable toxicity occurs.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Female patients, >/= 18 years of age
- •Histologically confirmed HER2-negative breast cancer
- •Disease progression during or following first-line treatment with Avastin and chemotherapy for locally recurrent or metastatic breast cancer
- •Avastin treatment in first-line setting must have been a minimum of 4 cycles (15 mg/kg) or 6 cycles (10 mg/kg) in combination with chemotherapy
- •ECOG performance status 0-2
- •At least 28 days since prior radiation therapy or surgery and recovery from treatment
排除标准
- •Anti-angiogenic therapy or anti-vascular endothelial growth factors other than Avastin for first-line treatment
- •Active malignancy other than superficial basal cell and superficial squamous cell carcinoma of the skin, or in situ carcinoma of the cervix or breast within the last 5 years
- •Inadequate renal function
- •Clinically relevant cardio-vascular disease
- •Known CNS disease except for treated brain metastases
- •Chronic daily treatment with high-dose aspirin (>325 mg/day) or clopidogrel (>75 mg/day)
- •Pregnant or lactating women
研究组 & 干预措施
1
干预措施: Chemotherapy (Drug)
2
干预措施: bevacizumab [Avastin] (Drug)
2
干预措施: Chemotherapy (Drug)
结局指标
主要结局
Percentage of Participants Estimated to be Alive and Free of Second-Line Disease Progression at Month 12
时间窗: Month 12
Second-line PFS was defined as the time from randomization to PD or death due to any cause during their second-line of treatment with bevacizumab and/or chemotherapy, whichever occurred first. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without secondline PD or death were censored at the date of last tumor assessment where non-progression was documented.
Percentage of Participants Estimated to be Alive and Free of Second-Line Disease Progression at Month 6
时间窗: Month 6
Second-line PFS was defined as the time from randomization to PD or death due to any cause during their second-line of treatment with bevacizumab and/or chemotherapy, whichever occurred first. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without second-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
Percentage of Participants Estimated to be Alive and Free of Second-Line Disease Progression at Month 18
时间窗: Month 18
Second-line PFS was defined as the time from randomization to PD or death due to any cause during their secondline of treatment with bevacizumab and/or chemotherapy, whichever occurred first. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without second-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
Percentage of Participants Estimated to be Alive and Free of Second-Line Disease Progression at Month 24
时间窗: Month 24
Second-line PFS was defined as the time from randomization to PD or death due to any cause during their second-line of treatment with bevacizumab and/or chemotherapy, whichever occurred first. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without second-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
Percentage of Participants With Second-Line Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)
时间窗: Baseline (less than or equal to [≤] 28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years
Second-line PFS was defined as the time from randomization to progressive disease (PD) or death due to any cause during their second-line of treatment with bevacizumab and/or chemotherapy, whichever occurred first. For target lesions (TLs), PD was defined at least a 20 percent (%) increase in the sum of the largest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of one or more new lesions. For non-target lesions (NTLs), PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without second-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
Second-Line PFS
时间窗: Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years
The median time, in months, from randomization to second-line PFS event. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without second-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
次要结局
- Second-Line PFS by Baseline Risk Factor (Data Cutoff 20 December 2013)(Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years)
- Percentage of Participants With a Second-Line Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) According to RECIST v1.1 (Data Cutoff 20 December 2013)(Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years)
- Percentage of Participants With a Second-Line CR, PR, Stable Disease, and PD According to RECIST v1.1 (Data Cutoff 20 December 2013)(Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years)
- Duration of Second-Line Objective Response (Data Cutoff 20 December 2013)(Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 3 years)
- Percentage of Participants With a Second-Line Documented CR or PR According to RECIST v1.1 Estimated to be Alive and Free of Disease Progression at Months 3, 6, and 9 (Data Cutoff 20 December 2013)(Months 3, 6, and 9)
- Percentage of Participants With Third-Line PFS According to RECIST v1.1(First dose of third-line treatment until PD or death due to any cause (assessed every 8-9 weeks, over a period of approximately 14 months))
- Third-Line PFS(First dose of third-line treatment until PD or death due to any cause (over a period of approximately 14 months))
- Percentage of Participants With Second- and Third-Line PFS According to RECIST v1.1(Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 4 years)
- Second- and Third-Line PFS(Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 4 years)
- Percentage of Participants With Second- and Third-Line Tumor Progression(Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 4 years)
- Time to Second- and Third-Line Tumor Progression(Baseline (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until approximately 4 years)
- Percentage of Participants Who Died(Baseline until death (up to approximately 4 years))
- Overall Survival (OS)(Baseline until death (up to approximately 4 years))
- Percentage of Participants Estimated to be Surviving at Months 6, 12, 18, and 24(Months 6, 12, 18, and 24)
- Percentage of Participants Experiencing Problems by European Quality of Life Instrument (EQ-5D) Category (Data Cutoff 20 December 2013)(Baseline, during second-line treatment at Weeks 8 and 16 (4-week cycles) or Weeks 9 and 18 (3-week cycles) and at second-line PD (up to approximately 3 years))
- Quality of Life Assessed As an Index Score Using the EQ-5D (Data Cutoff 20 December 2013)(Baseline, during second-line treatment at Weeks 8 and 16 (4-week cycles) or Weeks 9 and 18 (3-week cycles) and at second-line PD (up to approximately 3 years))
- Change From Baseline in EQ-5D Index Scores (Data Cutoff 20 December 2013)(Baseline, during second-line treatment at Weeks 8 and 16 (4-week cycles) or Weeks 9 and 18 (3-week cycles) and at second-line PD (up to approximately 3 years))
- Quality of Life Assessed Using the EQ-5D Visual Analogue Scale (VAS) Scores (Data Cutoff 20 December 2013)(Baseline, during second-line treatment at Weeks 8 and 16 (4-week cycles) or Weeks 9 and 18 (3-week cycles) and at second-line PD (up to approximately 3 years))
- Change From Baseline in VAS Scores (Data Cutoff 20 December 2013)(Baseline, during second-line treatment at Weeks 8 and 16 (4-week cycles) or Weeks 9 and 18 (3-week cycles) and at second-line PD (up to approximately 3 years))
- Functional Assessment of Cancer Therapy-Breast (FACT-B) Scores (Data Cutoff 20 December 2013)(Baseline (≤28 days after randomization), every 8-9 weeks thereafter until second-line PD (up to approximately 3 years))
- Change From Baseline in FACT-B Scores (Data Cutoff 20 December 2013)(Baseline (≤28 days after randomization), every 8-9 weeks thereafter until second-line PD (up to approximately 3 years))