A Randomized, Double-blind, Multi-center Phase 2 Trial of Denosumab in Combination With Chemotherapy as First-line Treatment of Metastatic Non-small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 226
- 试验地点
- 1
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This randomized phase 2 trial is studying the effect of adding denosumab to standard chemotherapy in the treatment of advanced lung cancer.
详细描述
This is a global randomized double-blind placebo-controlled study in patients with Stage IV untreated non-small cell lung cancer (NSCLC) with or without bone metastasis. Eligible participants are to receive 4 to 6 cycles of a standard of care platinum-doublet chemotherapy regimen. Participants will be randomized in a 2:1 ratio to receive denosumab or matching placebo with the first investigational product dose coinciding with participant's first cycle of chemotherapy and continuing until the primary analysis, unacceptable toxicity, withdrawal of consent, death, or lost to follow-up. Participants who discontinued the investigational product early (ie, before primary analysis) were followed for disease status and survival. The primary analysis took place when 149 events of death had been reported. All participants were followed for 2 years after the last dose of blinded investigational product.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed stage IV non-small cell lung carcinoma (NSCLC), according to 7th Tumor/Node/Metastasis (TNM) classification (cytological specimens obtained by bronchial washing or brushing, or fine-needle aspiration are acceptable)
- •Subject has available and has provided consent to release to the sponsor (or designee) a tumor block with confirmed tumor content (or approximately 20 unstained charged slides [a minimum of 7 slides is mandatory]) and the corresponding pathology report
- •Planned to receive 4 to 6 cycles of pemetrexed or gemcitabine in combination with cisplatin or carboplatin
- •For subjects to receive pemetrexed, planned to receive vitamin B12 and folate per pemetrexed approved labeling
- •Radiographically evaluable (measurable or non-measurable) disease (according to modified Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria
- •Other inclusion criteria may apply
排除标准
- •Known presence of documented sensitizing epidermal growth factor receptor (EGFR) activating mutation or echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation (screening following local standards, but strongly encouraged in non-squamous histology)
- •Known brain metastases (systematic screening of patients not mandatory)
- •Any prior systemic therapy (before randomization) for the treatment of NSCLC (including chemoradiation), except if for non-metastatic disease and was completed at least 6 months prior to randomization
- •Planned to receive bevacizumab
- •Significant dental/oral disease, including prior history or current evidence of osteonecrosis/ osteomyelitis of the jaw, or with the following:
- •Active dental or jaw condition which requires oral surgery
- •Non-healed dental/oral surgery
- •Planned invasive dental procedures for the course of the study.
研究组 & 干预措施
Placebo
Participants received placebo matching to denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.
干预措施: Zoledronic acid (Drug)
Placebo
Participants received placebo matching to denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.
干预措施: Placebo to Denosumab (Drug)
Placebo
Participants received placebo matching to denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.
干预措施: Standard Chemotherapy (Drug)
Denosumab
Participants received 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.
干预措施: Denosumab (Drug)
Denosumab
Participants received 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.
干预措施: Standard Chemotherapy (Drug)
Denosumab
Participants received 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.
干预措施: Placebo to Zoledronic Acid (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: From randomization until the end of study; median time on study was 9.64 months.
Overall survival was calculated as the time from the date of randomization to the date of death from any cause. Participants last known to be alive were censored at the last contact date.
次要结局
- Progression-free Survival (PFS)(From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.)
- Serum Denosumab Trough Levels in Participants Who Received Q4W Dosing(Prior to dosing at day 8 and weeks 4, 8, 12, 16, 20 and 24)
- Correlation of Tumor Tissue RANK Expression With Overall Survival(From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.)
- Correlation of Tumor Tissue RANK Ligand Expression With Overall Survival(From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.)
- Number of Participants With Treatment-emergent Adverse Events(From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively.)
- Correlation of Tumor Tissue RANKL Expression With Objective Response Rate(From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.)
- Clinical Benefit Rate(From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.)
- Correlation of Tumor Tissue RANK Expression With Objective Response Rate(From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.)
- Objective Response Rate(From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.)
- Serum Denosumab Trough Levels in Participants Who Received Q3W Dosing(Prior to dosing at day 8 and weeks 3, 6, 9, 12, 15, 18, 21 and 24.)