A Single Arm, Pilot Study of Ramipril for Preventing Radiation-Induced Cognitive Decline in Glioblastoma (GBM) Patients Receiving Brain Radiotherapy
概览
- 阶段
- 2 期
- 干预措施
- Ramipril
- 疾病 / 适应症
- Glioblastoma
- 发起方
- Wake Forest University Health Sciences
- 入组人数
- 75
- 试验地点
- 423
- 主要终点
- Efficacy of Ramipril of Neurocognitive Function at Baseline - Shipley Institute of Living Scale-Version 2 Vocabulary
- 状态
- 已完成
- 最后更新
- 上个月
概览
简要总结
This study is to determine if an oral drug called Ramipril can lower the chance of memory loss in patients with glioblastoma getting chemoradiation. Patients will take Ramipril during chemoradiation and continue until 4 months post-treatment. Memory loss will be assessed using several neurocognitive tests throughout the duration of the study.
详细描述
This is a pilot study of an oral drug Ramipril to prevent cognitive decline in glioblastoma patients receiving partial brain radiation and concurrent and adjuvant temozolomide . Ramipril will be titrated to the highest tolerable dose during chemoradiation (2.5-5 mg). Once this dose is determined, the patient will continue at this dose for 4 months after the completion of chemoradiation. Patients will be followed until 5 months post chemoradiation for compliance, toxicity, cognitive decline and participant reported outcomes (PRO).
研究者
入排标准
入选标准
- •Histologically proven diagnosis of glioblastoma or gliosarcoma (World Health Organization \[WHO\] grade IV) obtained at the time of a partial or gross total resection of the tumor. Patients who undergo a stereotactic needle biopsy alone are not eligible.
- •The tumor must have a supratentorial component.
- •History/physical examination within 14 days prior to enrollment.
- •The patient must have recovered from the effects of surgery, postoperative infection, and other complications before enrollment
- •Patient planning to receive brain RT, and concurrent and adjuvant temozolomide chemotherapy for six weeks as per standard of care therapy. Use of the Optune® (also known as Tumor Treating Fields or TTFields) device is allowed at provider discretion, but must begin after the Month 1 Post RT (10 week \[wk\]) Neurocognitive-PRO assessment.
- •Study drug (Ramipril) must be given \>= 21 days and ≤ 42 days after surgery.
- •All available brain magnetic resonance imaging (MRI) or computed tomography (CT) imaging reports from surgery to study completion must be submitted. This includes any post-operative or pre-radiation scan reports.
- •Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2
- •Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 (obtained within 14 days prior to enrollment)
- •Platelets \>= 100,000 cells/mm\^3 (obtained within 14 days prior to enrollment)
排除标准
- •Prior allergic reaction or intolerance to angiotensin-converting-enzyme (ACE) inhibitor
- •Hypotension (\< 110 mg Hg systolic) at the time of enrollment
- •Renal insufficiency with creatinine clearance of \< 40 ml/min (at time of enrollment)
- •Solitary kidney or known renal artery stenosis
- •Current ACE inhibitor or angiotensin receptor blocker use. Patients can come off ACE inhibitors or angiotensin receptor blockers for 1 week to be eligible for this study.
- •Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 2 years. (For example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible).
- •Recurrent or multifocal malignant gliomas
- •Metastases detected below the tentorium or beyond the cranial vault
- •Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable, except prior temozolomide. Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted.
- •Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields.
研究组 & 干预措施
Ramipril
Ramipril will be taken once daily by mouth. It will be titrated during the first 3 weeks of chemoradiation to the highest tolerable dose (2.5-5 mg). This dose will be taken each day until 4 months post-chemoradiation treatment (22 weeks).
干预措施: Ramipril
结局指标
主要结局
Efficacy of Ramipril of Neurocognitive Function at Baseline - Shipley Institute of Living Scale-Version 2 Vocabulary
时间窗: Baseline
Shipley Institute of Living Scale provides an assessment of premorbid intellectual functioning comparable to a verbal IQ and thus is a proxy for cognitive reserve. This vocabulary test requires respondents to read a target word and select one of four words that most closely means the same thing. The score is total correct of 40 items (0-40). Higher scores indicate a better outcome.
Change From Baseline Neurocognitive Function at 10 Weeks - Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall Standardized Score
时间窗: Baseline,10 weeks
HVLT-R measures verbal learning and memory. It consists of a 12-item word list which is read to subjects on three successive learning trials. Free recall scores are recorded for each learning trial. Scores for immediate recall (total of three trials), delayed recall (total number of words recalled after 20 minutes), and recognition (total number of words correctly identified) will be the variables derived from the HVLT-R. A raw score (0-36) for part A Total Recall is calculated as the total number of words correctly recalled amongst the three trials. Test scores are presented as standardized z scores (mean=0, sd=1) with infinite range. Higher standardized scores indicate better neurocognitive function. Change in standardized scores are compared with results from the control arm of RTOG0825 (NCT00884741).
Change From Baseline Neurocognitive Function at 10 Weeks - Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall Standardized Score
时间窗: Baseline,10 weeks
HVLT-R measures verbal learning and memory. It consists of a 12-item word list which is read to subjects on three successive learning trials. Free recall scores are recorded for each learning trial. Scores for immediate recall (total of three trials), delayed recall (total number of words recalled after 20 minutes), and recognition (total number of words correctly identified) will be the variables derived from the HVLT-R. A raw score (0-12) for part B Delayed Recall is calculated as the number of words correctly recalled. Test scores are presented as standardized z scores (mean=0, sd=1) with infinite range. Higher standardized scores indicate better neurocognitive function. Change in standardized scores are compared with results from the control arm of RTOG0825 (NCT00884741).
Change From Baseline Neurocognitive Function at 10 Weeks - Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recognition Standardized Score
时间窗: Baseline,10 weeks
HVLT-R measures verbal learning and memory. It consists of a 12-item word list which is read to subjects on three successive learning trials. Free recall scores are recorded for each learning trial. Scores for immediate recall (total of three trials), delayed recall (total number of words recalled after 20 minutes), and recognition (total number of words correctly identified) will be the variables derived from the HVLT-R. A raw score (-12-12) for part C Delayed Recognition is calculated as the number of incorrectly identified words subtracted from the number of correctly identified words. Test scores are presented as standardized z scores (mean=0, sd=1) with infinite range. Higher standardized scores indicate better neurocognitive function. Change in standardized scores are compared with results from the control arm of RTOG0825 (NCT00884741).
Change From Baseline Neurocognitive Function at 10 Weeks - Trail Making Test Part A (TMT A) Standardized Score
时间窗: Baseline,10 weeks
Part A of the TMT measures attention and visual motor skills and processing speed and requires subjects to connect 25 numbered circles in the proper sequence (1-2-3-…) as quickly as possible. The raw score for TMT-A is the total time in seconds required to complete the task. Scores can also be generated for number of errors and number of circles correctly connected. If the assessment was not completed in the allotted time, a prorated score was calculated based on the last completed correct circle. Final prorated raw scores of total time were at least 0 seconds with no maximum limit. Test scores are presented as standardized z scores (mean=0, sd=1) with infinite range. Higher standardized scores indicate better neurocognitive function. Change in standardized scores are compared with results from the control arm of RTOG0825 (NCT00884741).
Change From Baseline Neurocognitive Function at 10 Weeks - Trail Making Test Part B (TMT B) Standardized Score
时间窗: Baseline,10 weeks
TMT-B requires subjects to connect 25 dots in an alternating numerical and alphabetical sequence (1-A-2-B-…). TMT-B with its added complexity and set shifting requirements is a widely used measure of executive function. The raw score TMT-B is the total time in seconds required to complete the task. If the assessment was not completed in the allotted time, a prorated score was calculated based on the last completed correct circle. Final prorated raw scores of total time were at least 0 seconds with no maximum limit. Test scores are presented as standardized z scores (mean=0, sd=1) with infinite range. Higher standardized scores indicate better neurocognitive function. Change in standardized scores are compared with results from the control arm of RTOG0825 (NCT00884741).
Change From Baseline Neurocognitive Function at 10 Weeks - Controlled Oral Word Association Test (COWA) Standardized Scores
时间窗: Baseline,10 weeks
The COWA measures speed of mental processing, verbal fluency, and executive function. Subjects are asked to name as many words as possible all beginning with a specified letter. A total of three trials are administered, each with a different letter. The raw score on the COWA (0-87) is the total number of words named across the three trials minus repetitions. Test scores are presented as standardized z scores (mean=0, sd=1) with infinite range. Higher standardized scores indicate better neurocognitive function. Change in standardized scores are compared with results from the control arm of RTOG0825 (NCT00884741).
Retention Rate at 10 Weeks
时间窗: 10 weeks
Measured by the percent of patients who took 75% of the Ramipril doses and completed the neurocognitive battery of tests
次要结局
- Determine Presence of Apolipoprotein Epsilon (ApoE)(Baseline)
- Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Global HRQOL Scale(Baseline, 6 weeks, 10 weeks, 22 weeks)
- Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Physical Functioning Scale(Baseline, 6 weeks, 10 weeks, 22 weeks)
- Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Cognitive Functioning Scale(Baseline, 6 weeks, 10 weeks, 22 weeks)
- Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Social Functioning Scale(Baseline, 6 weeks, 10 weeks, 22 weeks)
- Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Motor Dysfunction(Baseline, 6 weeks, 10 weeks, 22 weeks)
- Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) - Communication Deficit(Baseline, 6 weeks, 10 weeks, 22 weeks)
- Number of Participants With Neurocognitive Decline- Hopkins Verbal Learning Test-Revised (HVLT-R) - Total Recall(Baseline - 22 weeks)
- Number of Participants With Neurocognitive Decline- Hopkins Verbal Learning Test-Revised (HVLT-R) - Delayed Recall(Baseline - 22 weeks)
- Number of Participants With Neurocognitive Decline- Hopkins Verbal Learning Test-Revised (HVLT-R) - Recognition(Baseline - 22 weeks)
- Number of Participants With Neurocognitive Decline- Trail Making Test Part A (TMT A)(Baseline - 22 weeks)
- Number of Participants With Neurocognitive Decline- Trail Making Test Part B (TMT B)(Baseline - 22 weeks)
- Number of Participants With Neurocognitive Decline- Controlled Oral Word Association Test (COWA)(Baseline - 22 weeks)
- Efficacy of Neurocognitive Function in Surviving Patients- Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall Standardized Score(22 weeks)
- Efficacy of Neurocognitive Function in Surviving Patients- Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall Standardized Score(22 weeks)
- Efficacy of Neurocognitive Function in Surviving Patients- Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recognition Standardized Score(22 weeks)
- Efficacy of Neurocognitive Function in Surviving Patients- Trail Making Test Part A (TMT A) Standardized Score(22 weeks)
- Efficacy of Neurocognitive Function in Surviving Patients- Trail Making Test Part B (TMT B) Standardized Score(22 weeks)
- Efficacy of Neurocognitive Function in Surviving Patients- Controlled Oral Word Association Test (COWA) Standardized Score(22 weeks)
- Efficacy of Neurocognitive Function in Surviving Patients- EORTCQLQ30/BN20 - Global HRQOL Scale(22 weeks)
- Efficacy of Neurocognitive Function in Surviving Patients- EORTCQLQ30/BN20 - Physical Functioning Scale(22 weeks)
- Efficacy of Neurocognitive Function in Surviving Patients- EORTCQLQ30/BN20 - Cognitive Functioning Scale(22 weeks)
- Efficacy of Neurocognitive Function in Surviving Patients- EORTCQLQ30/BN20 - Social Functioning Scale(22 weeks)
- Efficacy of Neurocognitive Function in Surviving Patients- EORTCQLQ30/BN20 - Motor Dysfunction(22 weeks)
- Efficacy of Neurocognitive Function in Surviving Patients- EORTCQLQ30/BN20 - Communication Deficit(22 weeks)