A Phase 2 Study of Nivolumab Plus Ipilimumab in RAI Refractory, Aggressive Thyroid Cancer With Exploratory Cohorts in Medullary and Anaplastic Thyroid Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 53
- 试验地点
- 1
- 主要终点
- Best Overall Response Rate
研究概览
简要总结
This research study is studying nivolumab, an investigational drug, in combination with ipilimumab, also an investigational drug, as a possible treatment for thyroid cancer.
The drugs involved in this study are:
- Nivolumab (Opdivo™)
- Ipilimumab (Yervoy™)
详细描述
This research study is a Phase 2 clinical trial. Phase 2 clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.
The purpose of this study is to evaluate effectiveness (how well the drug/s work) of nivolumab combined with ipilimumab.
Nivolumab and ipilimumab are types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack cancer cells. Nivolumab has been approved by the US Food and Drug Administration (FDA) for the treatment of metastatic melanoma (a type of skin cancer), and specific types of previously treated advanced lung and kidney cancers. Ipilimumab is approved by the FDA for the treatment of metastatic melanoma.
The combination of nivolumab and ipilimumab is now FDA approved as treatment for patients with metastatic melanoma. However, the use of nivolumab as well as ipilimumab alone or in combination for the treatment of patients with thyroid cancer is not approved
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
DTC - Nivolumab alone for two weeks
Differentiated Thyroid Cancer (DTC) participants received Ipilimumab 1mg/kg q6 weeks via IV infusion, starting two weeks after Nivolumab 3mg/kg q6 weeks.
干预措施: Nivolumab (Drug)
DTC - Nivolumab alone for two weeks
Differentiated Thyroid Cancer (DTC) participants received Ipilimumab 1mg/kg q6 weeks via IV infusion, starting two weeks after Nivolumab 3mg/kg q6 weeks.
干预措施: Ipilimumab (Drug)
DTC - Ipilimumab alone for two weeks
Differentiated Thyroid Cancer (DTC) participants received Nivolumab 3mg/kg q6 weeks via IV infusion, starting two weeks after Ipilimumab 1mg/kg q6 weeks.
干预措施: Nivolumab (Drug)
DTC - Ipilimumab alone for two weeks
Differentiated Thyroid Cancer (DTC) participants received Nivolumab 3mg/kg q6 weeks via IV infusion, starting two weeks after Ipilimumab 1mg/kg q6 weeks.
干预措施: Ipilimumab (Drug)
Differentiated Thyroid Cancer (Primary cohort)
Differentiated Thyroid Cancer (DTC) participants received Ipilimumab (Ipi) 1mg/kg q6 weeks and Nivolumab (Nivo) 3mg/kg q6 weeks sequentially either Ipi or Nivo first with 2 weeks apart prior to start of either Ipi or Nivo second.
Per protocol order in sequential design was not expected to impact efficacy rather was for exploratory correlative analyses. Participants were treated indefinitely until disease progression or withdrawal for other reasons.
干预措施: Nivolumab (Drug)
Differentiated Thyroid Cancer (Primary cohort)
Differentiated Thyroid Cancer (DTC) participants received Ipilimumab (Ipi) 1mg/kg q6 weeks and Nivolumab (Nivo) 3mg/kg q6 weeks sequentially either Ipi or Nivo first with 2 weeks apart prior to start of either Ipi or Nivo second.
Per protocol order in sequential design was not expected to impact efficacy rather was for exploratory correlative analyses. Participants were treated indefinitely until disease progression or withdrawal for other reasons.
干预措施: Ipilimumab (Drug)
Medullary Thyroid Cancer (Exploratory Cohort)
Medullary Thyroid Cancer (MTC) participants received Ipilimumab (Ipi) 1mg/kg q6 weeks and Nivolumab (Nivo) 3mg/kg q6 weeks sequentially either Ipi or Nivo first with 2 weeks apart prior to start of either Ipi or Nivo second, or started Ipi or Nivo together.
Per protocol order in sequential design was not expected to impact efficacy rather was for exploratory correlative analyses. Participants were treated indefinitely until disease progression or withdrawal for other reasons.
干预措施: Nivolumab (Drug)
Medullary Thyroid Cancer (Exploratory Cohort)
Medullary Thyroid Cancer (MTC) participants received Ipilimumab (Ipi) 1mg/kg q6 weeks and Nivolumab (Nivo) 3mg/kg q6 weeks sequentially either Ipi or Nivo first with 2 weeks apart prior to start of either Ipi or Nivo second, or started Ipi or Nivo together.
Per protocol order in sequential design was not expected to impact efficacy rather was for exploratory correlative analyses. Participants were treated indefinitely until disease progression or withdrawal for other reasons.
干预措施: Ipilimumab (Drug)
Anaplastic Thyroid Cancer (Exploratory Cohort)
Anaplastic Thyroid Cancer (ATC) participants received Ipilimumab (Ipi) 1mg/kg q6 weeks and Nivolumab (Nivo) 3mg/kg q6 weeks sequentially either Ipi or Nivo first with 2 weeks apart prior to start of either Ipi or Nivo second prior to study amendment or in combination from the start after study amendment due to aggressive nature of the disease in this cohort.
Per protocol order in sequential design was not expected to impact efficacy rather was for exploratory correlative analyses. Participants were treated indefinitely until disease progression or withdrawal for other reasons.
干预措施: Nivolumab (Drug)
Anaplastic Thyroid Cancer (Exploratory Cohort)
Anaplastic Thyroid Cancer (ATC) participants received Ipilimumab (Ipi) 1mg/kg q6 weeks and Nivolumab (Nivo) 3mg/kg q6 weeks sequentially either Ipi or Nivo first with 2 weeks apart prior to start of either Ipi or Nivo second prior to study amendment or in combination from the start after study amendment due to aggressive nature of the disease in this cohort.
Per protocol order in sequential design was not expected to impact efficacy rather was for exploratory correlative analyses. Participants were treated indefinitely until disease progression or withdrawal for other reasons.
干预措施: Ipilimumab (Drug)
MTC - Nivolumab alone for two week
Medullary Thyroid Cancer (MTC)participants received Ipilimumab 1mg/kg q6 weeks via IV infusion, starting two weeks after Nivolumab 3mg/kg q6 weeks.
干预措施: Nivolumab (Drug)
MTC - Nivolumab alone for two week
Medullary Thyroid Cancer (MTC)participants received Ipilimumab 1mg/kg q6 weeks via IV infusion, starting two weeks after Nivolumab 3mg/kg q6 weeks.
干预措施: Ipilimumab (Drug)
MTC - Ipilimumab alone for two weeks
Medullary Thyroid Cancer (MTC) participants received Nivolumab 3mg/kg q6 weeks via IV infusion, starting two weeks after Ipilimumab 1mg/kg q6 weeks.
干预措施: Nivolumab (Drug)
MTC - Ipilimumab alone for two weeks
Medullary Thyroid Cancer (MTC) participants received Nivolumab 3mg/kg q6 weeks via IV infusion, starting two weeks after Ipilimumab 1mg/kg q6 weeks.
干预措施: Ipilimumab (Drug)
ATC - Nivolumab alone for two week
Anaplastic Thyroid Cancer (ATC) received Ipilimumab 1mg/kg q6 weeks via IV infusion, starting two weeks after Nivolumab 3mg/kg q6 weeks.
干预措施: Nivolumab (Drug)
ATC - Nivolumab alone for two week
Anaplastic Thyroid Cancer (ATC) received Ipilimumab 1mg/kg q6 weeks via IV infusion, starting two weeks after Nivolumab 3mg/kg q6 weeks.
干预措施: Ipilimumab (Drug)
ATC - Ipilimumab alone for two week
Anaplastic Thyroid Cancer (ATC) received Nivolumab 3mg/kg q6 weeks via IV infusion, starting two weeks after Ipilimumab 1mg/kg q6 weeks.
干预措施: Nivolumab (Drug)
ATC - Ipilimumab alone for two week
Anaplastic Thyroid Cancer (ATC) received Nivolumab 3mg/kg q6 weeks via IV infusion, starting two weeks after Ipilimumab 1mg/kg q6 weeks.
干预措施: Ipilimumab (Drug)
ATC - Ipilimumab + Nivolumab
Anaplastic Thyroid Cancer (ATC) received Nivolumab 3mg/kg q6 weeks and Ipilimumab 1mg/kg q6 weeks via IV infusion.
干预措施: Nivolumab (Drug)
ATC - Ipilimumab + Nivolumab
Anaplastic Thyroid Cancer (ATC) received Nivolumab 3mg/kg q6 weeks and Ipilimumab 1mg/kg q6 weeks via IV infusion.
干预措施: Ipilimumab (Drug)
结局指标
主要结局
Best Overall Response Rate
时间窗: Median (range) treatment duration (days) of 163.0 (21.0-734.0) for DTC cohort, for MTC cohort was 58.0 (30.0-252.0), and for ATC cohort 135.5 (10.0-735.0).
Best overall response rate is defined as the percentage of participants who achieved Complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
次要结局
- Median Progression Free Survival(Median (range) follow-up (months) for DTC cohort was 24.0 (1.84 - 24.7), for MTC cohort was 24.0 (23.0-24.2), and for ATC cohort was 22.2 (0.46 - 26.1).)
- Overall Survival at 2 Years (OS2)(Median (range) follow-up (months) for DTC cohort was 24.0 (1.84 - 24.7), for MTC cohort was 24.0 (23.0-24.2), and for ATC cohort was 22.2 (0.46 - 26.1).)
- Treatment-Related Adverse Events Rate(AEs were assessed every two weeks on treatment and within 30 days after the last dose. Median (range) treatment duration (days) of 163.0 (21.0-734.0) for DTC cohort, for MTC cohort was 58.0 (30.0-252.0), and for ATC cohort 135.5 (10.0-735.0).)
研究者
Kartik Sehgal, MD
Kartik Sehgal, MD
Dana-Farber Cancer Institute