A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Evaluating the Efficacy of ABT-888 in Combination With Temozolomide Versus Temozolomide Alone in Subjects With Metastatic Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 346
- 主要终点
- Progression-Free Survival (PFS): Time to Event
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of ABT-888 in combination with temozolomide versus temozolomide alone in subjects with metastatic melanoma.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Histologically (or cytologically) confirmed metastatic melanoma.
- •Unresectable Stage III or Stage IV metastatic melanoma.
- •Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
- •Subjects with no history of brain metastases demonstrated by a baseline MRI, or subjects with a history of previously treated brain metastases who have history of operable/SRS treatable brain metastases and completed surgical resection/stereotactic radiosurgery with or without adjuvant whole brain radiation at least 28 days prior to Day 1; have baseline MRI that shows no evidence of active intercranial disease; have discontinued taking medications for symptom management of brain metastases at least 7 days prior to Day 1
- •28 days since prior anti-cancer therapy.
- •Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-
- •Adequate hematologic, renal and hepatic function.
- •Partial Thromboplastin Time (PTT) is <= 1.5 x upper normal limit of institution's normal range and international normalized ratio (INR) < 1.
- •Subject's with significant fluid retention may be allowed at the discretion of the investigator.
- •Life expectancy > 12 weeks.
- •Females must not be pregnant.
- •Voluntarily signed informed consent.
排除标准
- •Lactate Dehydrogenase (LDH) > 2 x Upper Limit of Normal (ULN).
- •Ocular malignant melanoma.
- •History of central nervous system metastases or leptomeningeal disease.
- •Prior treatment with Dacarbazine (DTIC) or Temozolomide (TMZ).
- •Prior DNA damaging agents or cytotoxic chemotherapy.
- •Prior Whole Brain Radiation Therapy (with exceptions).
- •Received an investigational agent within 28 days of study.
- •History of seizure disorder and/or taking medication for seizure disorder.
- •Active malignancy within the past 5 years, except cervical cancer in situ, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin.
- •Medical condition that would cause a high risk for toxicities.
研究组 & 干预措施
Placebo for ABT-888 BID + TMZ QD
Placebo for ABT-888 twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.
干预措施: temozolomide (Drug)
Placebo for ABT-888 BID + TMZ QD
Placebo for ABT-888 twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.
干预措施: Placebo (Other)
ABT-888 20 mg BID + TMZ QD
ABT-888 20 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.
干预措施: temozolomide (Drug)
ABT-888 20 mg BID + TMZ QD
ABT-888 20 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.
干预措施: ABT-888 (Drug)
ABT-888 40 mg BID + TMZ QD
ABT-888 40 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.
干预措施: temozolomide (Drug)
ABT-888 40 mg BID + TMZ QD
ABT-888 40 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.
干预措施: ABT-888 (Drug)
结局指标
主要结局
Progression-Free Survival (PFS): Time to Event
时间窗: Every Cycle (28 Days) until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.
PFS: the number of days from the date that the participant was randomized to the date the participant experienced a confirmed event of disease progression (radiological, as determined by the central imaging center; or clinical, as determined by the investigator), or to the date of death (all causes of mortality) if disease progression was not reached. All events were included whether the participant was still taking or had discontinued study drug. Events of death were included for participants who had not experienced a confirmed event of disease progression, provided the death occurred within 8 weeks of the last available disease progression assessment. The distribution of PFS, as determined by the central imaging center (radiological)/ investigator (clinical), was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% confidence intervals (95% CIs) for the quartiles for the PFS distribution are provided.
次要结局
- 12-Month Overall Survival (OS) Rate(Per protocol, survival was to be assessed every 4 weeks or as needed after participant is registered as off-study for up to 18 months. The maximum observed follow-up at the overall survival analysis time was 21.0 months.)
- 6-month Progression-Free Survival Rate(Every Cycle (28 Days) until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.)
- Time to Neurological/Brain Metastases Progression(Every 2 cycles (8 weeks) until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.)
- Objective Response Rate(Every 2 cycles (8 weeks) until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.)
- Disease Control Rate(Week 8)
- Time to Disease Progression(Every Cycle (28 Days), until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.)
- Overall Survival (OS): Time to Event(Per protocol, survival follow-up information was to be obtained every 3 months for up to 18 months after the final visit for the subject. The maximum observed follow-up at the overall survival analysis time was 21.0 months.)