A Randomized, Placebo Controlled Phase 3 Study of ABT-414 With Concurrent Chemoradiation and Adjuvant Temozolomide in Subjects With Newly Diagnosed Glioblastoma (GBM) With Epidermal Growth Factor Receptor (EGFR) Amplification (Intellance1)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 691
- 试验地点
- 212
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This study seeks to determine whether the addition of ABT-414 to concomitant radiotherapy and temozolomide (TMZ) followed by combination of ABT-414 with adjuvant TMZ prolongs overall survival (OS) among participants with newly diagnosed glioblastoma (GBM) with epidermal growth factor receptor (EGFR) amplification.
In addition, there is a Phase 1, open-label, multicenter sub-study to assess the pharmacokinetics, safety and tolerability of ABT-414 in participants with newly diagnosed EGFR-amplified GBM who have mild or moderate hepatic impairment.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
Sub-study was open-label.
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
- •Must have a clinical diagnosis of glioblastoma (GBM).
- •Must have a confirmed epidermal growth factor receptor amplification in tumor tissue.
- •Must have a Karnofsky Performance Status (KPS) >= 70 at assessment <= 14 days prior to randomization (N/A to the sub-study).
- •Must have recovered from effects of surgery, postoperative infection and other complications of surgery.
- •Must have adequate bone marrow, renal, and hepatic function (For the sub-study, the participant must have adequate bone marrow and renal function and have mild-to-moderate hepatic impairment).
排除标准
- •Multifocal, recurrent or metastatic GBM or gliomatosis cerebri (For the sub-study, the participant can have multifocal GBM and glimatosis cerebri but can't have recurrent or metastatic GBM).
- •Prior chemo therapy or radiosensitizer for head and neck cancer.
- •Prior radiotherapy to the head or neck in overlap of radiation fields.
- •Prior therapy for glioblastoma or other invasive malignancy.
- •Prior, concomitant or planned treatment with Novo Tumor Treatment Fields (Novo-TTF), EGFR-targeted therapy, bevacizumab, Gliadel wafers or other intratumoral or intracavity anti-neoplastic therapy.
研究组 & 干预措施
Depatuxizumab Mafodotin, Radiation and Temozolomide (TMZ)
Depatuxizumab mafodotin is given on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Depatuxizumab mafodotin is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase.
干预措施: Temozolomide (Drug)
Depatuxizumab Mafodotin, Radiation and Temozolomide (TMZ)
Depatuxizumab mafodotin is given on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Depatuxizumab mafodotin is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase.
干预措施: Depatuxizumab mafodotin (Drug)
Depatuxizumab Mafodotin, Radiation and Temozolomide (TMZ)
Depatuxizumab mafodotin is given on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Depatuxizumab mafodotin is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase.
干预措施: Radiation (Radiation)
Placebo, Radiation and TMZ
Placebo is given on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Placebo is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase.
干预措施: Temozolomide (Drug)
Placebo, Radiation and TMZ
Placebo is given on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Placebo is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase.
干预措施: Radiation (Radiation)
Placebo, Radiation and TMZ
Placebo is given on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Placebo is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase.
干预措施: Placebo for ABT-414 (Drug)
Open-Label Sub-Study: Depatuxizumab Mafodotin, Radiation and TMZ
Depatuxizumab mafodotin is given to participants with hepatic impairment on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Depatuxizumab mafodotin is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase.
干预措施: Temozolomide (Drug)
Open-Label Sub-Study: Depatuxizumab Mafodotin, Radiation and TMZ
Depatuxizumab mafodotin is given to participants with hepatic impairment on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Depatuxizumab mafodotin is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase.
干预措施: Depatuxizumab mafodotin (Drug)
Open-Label Sub-Study: Depatuxizumab Mafodotin, Radiation and TMZ
Depatuxizumab mafodotin is given to participants with hepatic impairment on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Depatuxizumab mafodotin is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase.
干预措施: Radiation (Radiation)
结局指标
主要结局
Overall Survival (OS)
时间窗: Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).
Time to OS is defined as the number of days from the date of randomization to the date of death due to any cause.
次要结局
- OS for the MGMT Methylated Group(Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).)
- OS for the O6-methylguaninemethlytransferese (MGMT) Unmethylated Group(Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).)
- OS for the Epidermal Growth Factor Receptor (EGFR)vIII-Mutated Tumor Subgroup(Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).)
- Progression-Free Survival (PFS)(Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).)
- PFS for EGFRvIII-Mutated Tumor Subgroup(Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).)
- Deterioration Free Survival in M.D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) Symptom Severity Score(Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).)
- Deterioration Free Survival in MDASI-BT Symptom Interference Score(Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).)
- Deterioration Free Survival in Neurocognitive Functioning on the Hopkins Verbal Learning Test Revised (HVLT-R) Total Recall Score(Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).)