A Randomized, Double-Blind, Phase 2, Dose-Ranging Study to Evaluate the Safety and Efficacy of Veliparib and Whole Brain Radiation Therapy Versus Placebo and Whole Brain Radiation Therapy in Subjects With Brain Metastases From Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 307
- 主要终点
- Overall Survival
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy and safety of veliparib and whole brain radiation therapy in adults with brain metastases from non-small cell lung cancer (NSCLC).
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject must have cytologically or histologically confirmed non-small cell lung cancer
- •Subject must have brain metastases demonstrated on a magnetic resonance imaging (MRI) brain scan.
- •Subject must be eligible for treatment with WBRT
- •Subject must have had adequate hematologic, renal, and hepatic function.
排除标准
- •Subject is diagnosed with brain metastases greater than 28 days prior to Day 1
- •Subject received any prior form of cranial radiation and/or neurosurgery for their brain metastases
- •Subject's last dose of anti-cancer therapy or investigational therapy was less than or equal to 7 days prior to Day 1
- •Subject has a Karnofsky Performance Score of less than 70
- •Subject has significant dyspnea requiring supplemental oxygen therapy
- •Subject has liver metastases (restaging is not required for known liver metastases)
- •Subject has more than 2 sites (organ systems) of metastases from non-small cell lung cancer with the exception of intra-cranial sites of metastases from non-small cell lung cancer, thoracic sites of metastases from non-small cell lung cancer and bone metastases
- •Subject has leptomeningeal metastases or subarachnoid spread of tumor
- •Subject has unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or prior anti-cancer treatment
- •Subject has a known seizure disorder that is uncontrolled, or has seizures occurring greater than or equal to 3 times a week over the past month. Subjects presenting with symptoms of seizures from the brain metastases are eligible; however he/she should receive adequate anti-seizure medication prior to study treatment
- •Subject is pregnant or lactating
- •Subject has previously been treated with a poly-(ADP-ribose)-polymerase inhibitor as an investigational agent
- •Subject has clinically significant and uncontrolled major medical condition(s)
- •Subject has a history of another active cancer within the past 5 years except: cervical cancer in situ, in situ carcinoma of the bladder, basal or squamous cell carcinoma of the skin or other cancer in situ that is considered cured
研究组 & 干预措施
Placebo BID + WBRT
Participants received placebo twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.
干预措施: Placebo (Drug)
Veliparib 200 mg BID + WBRT
Participants received veliparib 200 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.
干预措施: Veliparib (Drug)
Veliparib 200 mg BID + WBRT
Participants received veliparib 200 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.
干预措施: Whole brain radiation therapy (Radiation)
Veliparib 50 mg BID + WBRT
Participants received veliparib 50 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.
干预措施: Veliparib (Drug)
Veliparib 50 mg BID + WBRT
Participants received veliparib 50 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.
干预措施: Whole brain radiation therapy (Radiation)
Placebo BID + WBRT
Participants received placebo twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.
干预措施: Whole brain radiation therapy (Radiation)
结局指标
主要结局
Overall Survival
时间窗: From randomization up to 36 months
Overall survival was defined as the number of days from the date of randomization to the date of death. All events of death were included, regardless of whether the event occurred while the participant was still taking study treatment or after treatment was discontinued. If a participant had not died, the data were censored at the date the participant was last known to be alive.
次要结局
- Time to Intracranial Progression (Radiographic)(From randomization up to 24 months)
- Best Tumor Response Rate(From randomization up to 24 months)
- Time to Clinical Brain Metastasis Progression(From randomization up to 24 months)