A Phase II Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 127
- 试验地点
- 45
- 主要终点
- Groups 1 and 2: Progression-free survival rate
研究概览
简要总结
The purpose of this research study is to find out whether adding an experimental vaccine called rindopepimut (also known as CDX-110) to the commonly used drug bevacizumab can improve progression free survival (slowing the growth of tumors) of patients with relapsed EGFRvIII positive glioblastoma.
详细描述
This Phase II study will enroll patients into three groups. Group 1 are patients who have never been treated with bevacizumab. These patients will be randomly assigned to receive either rindopepimut/GM-CSF or KLH, each along with bevacizumab. Treatment assignment for Group 1 will be blinded. Group 2 and Group 2C patients are those who are refractory to bevacizumab (experienced recurrence or progression of glioblastoma while on bevacizumab or within 2 months of discontinuing bevacizumab). These patients will all receive rindopepimut/GM-CSF along with bevacizumab. Patients will be treated until disease progression or intolerance and all patients will be followed for survival. Patients may be treated with other therapies that are not part of the study after discontinuing treatment with the study vaccine.
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)
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
- •Among other criteria, patients must meet the following conditions to be eligible for the study:
- •Age ≥18 years of age.
- •Histologic diagnosis of glioblastoma (WHO Grade IV).
- •Documented EGFRvlll positive tumor status (central lab confirmation).
- •First or second relapse of de novo glioblastoma or first diagnosis or first relapse of secondary glioblastoma.
- •Previous treatment must include surgery, conventional radiation therapy and temozolomide (TMZ).
- •Screening MRI must be obtained at least 4 weeks after any salvage surgery, and at least 12 weeks after radiation therapy.
- •KPS of ≥ 70%.
- •If applicable, systemic corticosteroid therapy must be at a dose of ≤ 4 mg of dexamethasone or equivalent per day during the week prior to Day
- •Evaluable disease in Groups 1 and 2; measurable disease in Group 2C
- •Life expectancy > 12 weeks.
- •Patients in Group 2 and 2C must have had disease progression while receiving bevacizumab or within 2 months of treatment with bevacizumab.
排除标准
- •Among other criteria, patients who meet the following conditions are NOT eligible for the study:
- •Subjects unable to undergo an MRI with contrast.
- •History, presence, or suspicion of metastatic disease
- •Prior receipt of vaccination against EGFRvIII.
- •Any known contraindications to receipt of study drugs, including known allergy or hypersensitivity to keyhole limpet hemocyanin (KLH), GM-CSF (sargramostim; LEUKINE®), polysorbate 80 or yeast derived products, or a history of anaphylactic reactions to shellfish proteins.
- •Use of non-protein based investigational therapy within 14 days prior to Day 1 or use of antibody-based investigational therapy within 28 days prior to Day
- •Clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment
- •Evidence of recent hemorrhage on screening MRI of the brain
- •Evidence of current drug or alcohol abuse.
- •Patients in Group 1 must not have received prior treatment with bevacizumab.
研究组 & 干预措施
Group 1a: Bevacizumab Naïve with Bevacizumab + rindopepimut.
About half of the patients who have never received treatment with bevacizumab will receive rindopepimut/GM-CSF in a blinded fashion in combination with bevacizumab.
干预措施: Bevacizumab (Drug)
Group 1a: Bevacizumab Naïve with Bevacizumab + rindopepimut.
About half of the patients who have never received treatment with bevacizumab will receive rindopepimut/GM-CSF in a blinded fashion in combination with bevacizumab.
干预措施: Rindopepimut (CDX-110) with GM-CSF (Drug)
Group 1b: Bevacizumab Naïve with Bevacizumab + KLH control
About half of the patients who have never received treatment with bevacizumab will receive KLH in a blinded fashion in combination with bevacizumab.
干预措施: Bevacizumab (Drug)
Group 1b: Bevacizumab Naïve with Bevacizumab + KLH control
About half of the patients who have never received treatment with bevacizumab will receive KLH in a blinded fashion in combination with bevacizumab.
干预措施: KLH (Drug)
Group 2 and 2C: Refractory to Bevacizumab
Patients with progressive disease while currently on or within two months after discontinuing bevacizumab will be administered rindopepimut/GM-CSF while continuing (or restarting if they had stopped bevacizumab).
干预措施: Bevacizumab (Drug)
Group 2 and 2C: Refractory to Bevacizumab
Patients with progressive disease while currently on or within two months after discontinuing bevacizumab will be administered rindopepimut/GM-CSF while continuing (or restarting if they had stopped bevacizumab).
干预措施: Rindopepimut (CDX-110) with GM-CSF (Drug)
结局指标
主要结局
Groups 1 and 2: Progression-free survival rate
时间窗: 6 months post-Day 1
Evaluate the antitumor activity of rindopepimut in adult patients with relapsed glioblastoma, as measured by the progression-free survival rate at 6 months post-Day 1 (PFS 6).
Group 2C: Objective Response Rate
时间窗: Every 8 weeks from Day 1 through progression or initiation of other anti-cancer therapy
Evaluate the anti-tumor activity of rindopepimut in adult patients with relapsed glioblastoma, as measured by the objective response rate (ORR) for patients with measurable disease at study entry.
次要结局
- Safety and Tolerability(Until 28 days or initiation of other anti-cancer treatment, whichever is first)
- Anti-tumor activity(During treatment and every 8 weeks through follow up)
- EGFRvIII-specific immune response(Several times during the first month of treatment and then approximately every 8 weeks until treatment is stopped.)