Ipilimumab Induction in Patients With Melanoma Brain Metastases Receiving Stereotactic Radiosurgery
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Local Control Rate
研究概览
简要总结
This is a study to test the efficacy of using standard immune therapy for melanoma prior to stereotactic radiosurgery (ipilimumab induction), as compared to stereotactic radiosurgery followed by immune therapy. The study's hypothesis is that ipilimumab induction is as good as or better than controlling brain metastases as compared to stereotactic radiosurgery followed by immune therapy.
详细描述
This is a randomized Phase II selection study investigating the use of ipilimumab induction prior to stereotactic radiosurgery (SRS), versus no induction, for melanoma brain metastases. Participants will be randomized to Arm A "Induction" (two doses of ipilimumab prior to SRS, two doses of ipilimumab after SRS) versus Arm B "No induction" (SRS first, followed by 4 doses of ipilimumab). Participants will undergo multiple dynamic contrast-enhanced MRIs of the brain and submit blood samples for immune testing.
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
- None
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
- •Patients with a histologically-confirmed diagnosis of melanoma who have imaging findings suggestive of 1 to 4 brain metastases
- •At least one lesion in the brain that is measurable, which is defined as ≥5 x 5mm (Prior craniotomy and surgical resection is allowed, as long as there is at least one remaining measurable lesion in the brain)
- •Patients must be candidates for stereotactic radiosurgery (SRS) and planning to undergo SRS
- •Patients must be candidates for ipilimumab as determined by the treating physician
- •Patients must be neurologically asymptomatic, or very minimally symptomatic, as judged by the treating physicians
- •At least 3 weeks has elapsed from any prior therapy, and the patient has recovered from side effects to ≤ grade 1 toxicities per Common Terminology Criteria (CTC) for Adverse Events
- •Age > or = 18 years old
- •Performance status of ECOG of 0 or 1 (ECOG is the Eastern Oncology Cooperative Group Scoring system used to quantify cancer patients' general well-being and activities of daily life; scores range from 0 to 5 where 0 is perfect health and 5 is death)
- •Adequate organ and marrow function: alanine aminotransferase (ALT ) < 2.5x's upper limit of normal (ULN) of the institutional normal reference range, aspartate aminotransferase (AST) < 2.5x's ULN of the institutional normal reference range, Bilirubin < 1.5x's ULN of the institutional normal reference range, Creatinine < 2.0 milligrams per deciliter, Platelets > 50,000 per microliter
- •Women of child-bearing potential must agree to use adequate contraception, defined as complete abstinence from intercourse with men or two methods
- •Ability to understand and the willingness to sign a written informed consent
排除标准
- •Previous radiotherapy to the lesion(s) of interest, including prior treatment with whole brain radiation therapy (WBRT). Prior treatment with SRS is allowed if the index lesion(s) is in a different, non-contiguous location than the previously treated lesion.
- •Patients who have previously received ipilimumab, PD-1 inhibitors or PD-L1 inhibitors are excluded due to the potential of effects on primary outcome
- •Patients who require WBRT or surgery at the time of enrollment
- •Neurologic symptoms or imaging findings that necessitate the use of steroids on the day of enrollment or in the prior 7 days
- •Highly suspicious magnetic resonance imaging (MRI) or cerebrospinal fluid evidence of leptomeningeal metastases, unless all measurable disease is localized and SRS is considered the treatment of choice
- •Concurrent treatment with any other anti-neoplastic drug or concurrent participation in another therapeutic clinical trial
- •Patients unable to undergo or tolerate MRI scans (presence of cardiac pacemaker, implanted cardiac defibrillator, aneurysm clips, history of allergic reaction/hypersensitivity to gadolinium)
- •Women who are pregnant or are nursing
- •Patients with absolute lymphocyte count of <500 cells/microliter, who are known to be HIV positive, who have clinically significant active autoimmune disease, or are receiving immunosuppression following solid organ or stem cell transplant
研究组 & 干预措施
B: No induction
Participants will undergo stereotactic radiosurgery (SRS) followed 2-3 weeks later by ipilimumab, which is given once every 3 weeks for a total of 4 doses.
干预措施: Ipilimumab (Drug)
B: No induction
Participants will undergo stereotactic radiosurgery (SRS) followed 2-3 weeks later by ipilimumab, which is given once every 3 weeks for a total of 4 doses.
干预措施: Stereotactic Radiosurgery (Procedure)
A: Induction
Patients will receive 2 doses of ipilimumab, which is given once every 3 weeks, prior to stereotactic radiosurgery (SRS), followed by 2 more doses of ipilimumab, for a total of 4 doses.
干预措施: Ipilimumab (Drug)
A: Induction
Patients will receive 2 doses of ipilimumab, which is given once every 3 weeks, prior to stereotactic radiosurgery (SRS), followed by 2 more doses of ipilimumab, for a total of 4 doses.
干预措施: Stereotactic Radiosurgery (Procedure)
结局指标
主要结局
Local Control Rate
时间窗: 6 months
The number of patients in each arm who are free from progression in the index (radiated) lesions in the brain at 6 months. Immune related response criteria was used to assess response to treatment. Immune-related Progressive Disease (irPD) in this trial is defined as an increase in tumor burden ≥25% relative to nadir (minimum recorded tumor burden), with confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented.
次要结局
- Overall Survival Rate(Up to 5 years)
- Regional (Intracranial) Control Rate(6 months)
- Intracranial Response Rate(Up to 12 months)
- Time to Progression(From date of enrollment to up to 2 years)