Testing Ramipril to Prevent Memory Loss in People with Glioblastoma
Brain & Spinal Cord Tumor
18 Years and older, Male and Female
WF-1801 (primary)
WF-1801
WF-1801
NCI-2018-01807
Summary
This phase II trial studies how well ramipril works in preventing cognitive decline in patients with glioblastoma or gliosarcoma who are undergoing brain radiation therapy and chemotherapy with temozolomide. Adding ramipril to standard of care treatment may help to lower the chance of memory loss.
Objectives
PRIMARY OBJECTIVES:
I. To assess the retention rate of patients at 10 weeks of ramipril treatment (6 weeks during radiation therapy [RT] and 4 weeks post RT) to determine whether or not we should proceed to a subsequent randomized study.
II. To estimate the effect of 10 weeks of ramipril on neurocognitive function in patients with glioblastoma (GBM) receiving chemoradiotherapy.
SECONDARY OBJECTIVES:
I. To estimate the time to neurocognitive decline with GBM receiving chemoradiotherapy and ramipril.
II. To estimate the effect of treatment with ramipril on and variability of specific non-memory cognitive functions including attention, executive function, visuo-motor skills, working memory, a screening measure of global cognitive function, mood, quality of life, fatigue and sleep disturbance.
III. To collect preliminary data on the presence of apolipoprotein epsilon (ApoE) isoform 4 serum (peripheral blood lymphocyte) test positivity as measured by quantitative polymerase chain reaction (PCR).
IV. To estimate neurocognitive function in surviving patients at the 4 month post RT endpoint.
V. To estimate response as reported by treating physician assessments.
EXPLORATORY OBJECTIVE:
I. To explore any subgroup differences for all secondary objectives measured at the post-RT 4 month visit by whether the patient received Optune (also known as Tumor-Treating Fields or TTFields) as part of their standard treatment following RT.
OUTLINE:
Beginning with standard of care RT and chemotherapy with temozolomide, patients receive ramipril orally (PO) once daily (QD) for 22 weeks (4 months post RT) in the absence of disease progression or unacceptable toxicity. After 1 month post RT, use of the Optune device may be used at the discretion of the treating physicians as per standard of care guidelines, timing and training. Patients also undergo collection of blood during screening and magnetic resonance imaging (MRI) or computed tomography (CT) scan throughout the trial.
Eligibility
- 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 6 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-Patient-Reported Outcome (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
- Age >= 18
- 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)
- Hemoglobin >= 10.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 10.0 g/dl is acceptable) (obtained within 14 days prior to enrollment)
- Blood urea nitrogen (BUN) =< 30 mg/dl within 14 days prior to enrollment
- Creatinine =< 1.7 mg/dl within 14 days prior to enrollment
- Total bilirubin =< 2.0 mg/dl within 14 days prior to enrollment
- Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 3 x normal range within 14 days prior to enrollment
- Patient must provide study specific informed consent prior to study entry
- Baseline potassium level < 5.0 mEq/L. High potassium values that are thought to be a result of sample hemolysis may be repeated to determine an accurate potassium level and to determine potential study eligibility. Likewise high potassium values thought to be a result of potassium supplementation may be repeated at an appropriate time (5 half-lives after supplement discontinuation) to determine potential study eligibility
- Patient must be able to complete neurocognitive tests in the English language as they are not validated in other languages at this time
- Women of childbearing potential and male participants must practice adequate contraception
- For females of child-bearing potential, negative serum or urine pregnancy test within 14 days of enrollment
- Local site must be able to follow the standard GBM radiation treatment dosimetry plan
- For patients who will be treated with the Optune device in addition to standard of care radiation plus concurrent and adjuvant temozolomide, the following inclusion criteria also apply:
* Patients must have only a supratentorial glioblastoma
* The treating physician must be a qualified provider having successfully completed the training course provided by Novocure, the device manufacturer
- Patients with prior malignancies if all treatment for that malignancy was completed at least 2 years before registration and the patient has no evidence of disease
Treatment Sites in Georgia
1100 Johnson Ferry Road
Suite 600
Sandy Springs, GA 30342
404-256-4777 ext 9242
www.gacancer.com
960 Johnson Ferry Road
Suite 130
Atlanta, GA 30342
404-303-3355
www.ugynonc.com
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts...
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