A Randomized Phase II Trial of Pertuzumab in Combination With Trastuzumab With or Without Chemotherapy, Both Followed by T-DM1 in Case of Progression, in Patients With HER2-positive Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 208
- 试验地点
- 71
- 主要终点
- Overall survival (OS) - Analysis Population: ITT Population 1
研究概览
简要总结
In HER2-positive metastatic breast cancer, trastuzumab based treatment is the standard of care as long as there are no contraindications to trastuzumab. Frequently, trastuzumab is being combined with taxanes in the first-line setting. However, since therapy with trastuzumab is active even in the absence of chemotherapy in HER2-positive MBC, the optimal treatment strategy either in combination or in sequence with chemotherapy is still under debate. This randomized phase II trial is studying a new strategy for the treatment of metastatic breast cancer with HER2-positive. First-line treatment consists of trastuzumab and pertuzumab, a treatment without chemotherapy. In case of disease progression, chemotherapy with T-DM1 is then performed as second-line treatment. Third-line and further line therapies are performed according to the physician's discretion. If this new therapeutic strategy is as effective and better tolerated than the conventional strategy, this would mean a serious breakthrough in the treatment of HER2-positive metastatic breast cancer.
详细描述
OBJECTIVES:
Primary
-To evaluate the efficacy in terms of overall survival (OS) at 24 months of a chemotherapy-free dual HER2-inhibition with trastuzumab and pertuzumab (first-line) followed by T-DM1 (second-line) and of a chemotherapy-containing dual HER2-inhibition with trastuzumab and pertuzumab (first-line) followed by T-DM1 (second-line) in patients with HER2-positive metastatic breast cancer.
Secondary
- To evaluate other efficacy parameter
- To evaluate the safety and tolerability profile of the two treatment strategies
- To evaluate the Quality of Life (QoL)
- To learn how patients are treated after trial treatment
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1
First line therapy: Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine Second line therapy: T-DM1
干预措施: Pertuzumab (Drug)
Trastuzumab, Pertuzumab, T-DM1
First line therapy: Trastuzumab, Pertuzumab Second line therapy: T-DM1
干预措施: Trastuzumab (Drug)
Trastuzumab, Pertuzumab, T-DM1
First line therapy: Trastuzumab, Pertuzumab Second line therapy: T-DM1
干预措施: Pertuzumab (Drug)
Trastuzumab, Pertuzumab, T-DM1
First line therapy: Trastuzumab, Pertuzumab Second line therapy: T-DM1
干预措施: T-DM1 (Drug)
Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1
First line therapy: Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine Second line therapy: T-DM1
干预措施: Trastuzumab (Drug)
Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1
First line therapy: Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine Second line therapy: T-DM1
干预措施: Paclitaxel (Drug)
Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1
First line therapy: Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine Second line therapy: T-DM1
干预措施: Vinorelbine (Drug)
Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1
First line therapy: Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine Second line therapy: T-DM1
干预措施: T-DM1 (Drug)
结局指标
主要结局
Overall survival (OS) - Analysis Population: ITT Population 1
时间窗: 24 months
Patients being alive 24 months after randomization. A success is considered if a patient is alive at least 24 months after randomization. Analysis Population: ITT Population 1
次要结局
- OS - Analysis Population: ITT Population 2(24 months)
- Progression Free Survival (PFS) of first-line treatment ignoring first Central Nervous System (CNS) lesion(10 / 16 months (PFS will be calculated sustained from randomization until documented PD (ignoring first CNS lesion) or death, whichever occurs first during first-line treatment ))
- PFS of second-line treatment ignoring first CNS lesion(9 months (PFS will be calculated sustained from registration of second line treatment until documented PD (ignoring first CNS lesion) or death, whichever occurs first during second-line treatment))
- DC of second-line treatment (based on investigator assessment)(6 months (DC is defined as the response CR, PR or SD for 6 months after registration of second-line treatment))
- AEs grade ≥2 until first progression (ignoring first CNS lesion)(Throughout first-line treatment (estimated up to 16 months))
- PFS of second-line treatment(8 months (PFS will be calculated sustained from registration of second line treatment until documented PD, PD CNS or death, whichever occurs first during second-line treatment))
- Time to failure of strategy (TFS) of first- plus second-line treatment(18 / 24 months (TFS will be calculated sustained from randomization until documented PD, PD CNS or death, whichever occurs first before starting third-line therapy ))
- OR of second-line treatment (based on investigator assessment)(9 months (OR is defined as the best status of response CR or PR after registration for second-line treatment up to second progression or start of a new treatment))
- Adverse events (AEs) according to the NCI CTCAE v4.0 of first-line treatment(Throughout first-line treatment (estimated up to 16 months))
- Overall survival OS(OS will be calculated from randomization until death (estimated median: 32 months))
- Objective response (OR) of first-line treatment (based on investigator assessment)(10 / 16 months (OR is defined as the best status of response CR or PR up to first progression or start of a new treatment))
- Disease control (DC) of first-line treatment (based on investigator assessment)(6 months (DC is defined as CR, PR or SD for 6 months after randomization and no PD at 6 month after randomization))
- AEs according to the NCI CTCAE v4.0 of second-line treatment(Throughout second-line treatment (estimated up to 9 months))
- Quality of Life (QoL)(At baseline and every 12 weeks (three-monthly) until progression or up to a maximum of 24 months during 1st line therapy. Within 3 weeks prior to registration, after 12 and 24 weeks during 2nd line therapy.)
- PFS of third-line treatment(4 months)