Testing Ramipril to Prevent Memory Loss in People With Glioblastoma

Glioblastoma Clinical Trial

Official title:

A Single Arm, Pilot Study of Ramipril for Preventing Radiation-Induced Cognitive Decline in Glioblastoma (GBM) Patients Receiving Brain Radiotherapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03475186
• Other study ID #: IRB00053531
• Secondary ID: 3UG1CA189824-04S
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 25, 2019
• Est. completion date: July 31, 2024

Study information

• Verified date: February 2024
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 75
• Est. completion date: July 31, 2024
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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)

• 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

• 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 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.

Exclusion Criteria:

• 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.

• Severe active co-morbidity, defined as follows:

• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of enrollment

• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of enrollment.

• Known HIV positivity or acquired immune deficiency syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.

• Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity.

• Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.

• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.

• Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study unless they involve standard of care or over the counter therapies or do not involve a drug therapy.

• Patients planning to receive therapeutic antitumor agents (excluding use of the Tumor Treating Fields (TTFields or Optune®) device after the Month 1 Post RT (10 wk) Neurocognitive-PRO assessment.) in addition to standard radiation and concurrent and adjuvant temozolomide are not eligible to participate in this study.

• Patients with impaired decision-making capacity; this exclusion is necessary because such patients may not be able to adequately give informed consent.

• Pregnant or lactating women, due to possible adverse effect on the developing fetus or infant due to study drug.

• For patients who will be treated with the Optune® device in addition to standard of care radiation plus concurrent and adjuvant temozolomide, the following exclusion criteria also apply:

• Optune® is not permitted in patients who have an active implanted medical device, skull defect (such as, missing bone with no replacement) or bullet fragments. Examples of active electronic devices include deep brain stimulators, spinal cord stimulators, vagus nerve stimulators, pacemakers, defibrillators, and programmatic shunts.

• Optune® is not permitted in patients who are known to be sensitive to conductive hydrogels. Examples of conductive hydrogels are gels used on electrocardiogram (ECG) stickers or transcutaneous electrical nerve stimulation (TENS) electrodes.

• Patients being treated with Memantine, Donepezil, and/or medications prescribed to enhance cognition.

Related Conditions & MeSH terms

• Chemoradiation
• Cognitive Decline
• Cognitive Dysfunction
• Glioblastoma
• Radiotherapy; Complications

Intervention

Drug:
• Ramipril
2.5 - 5 mg oral, 1x daily for 22 weeks

Locations

Country	Name	City	State
Guam	FHP Health Center-Guam	Tamuning
United States	Hawaii Cancer Care - Savio	'Aiea	Hawaii
United States	Hawaii Cancer Care - Westridge	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Queen's Cancer Center - Pearlridge	'Aiea	Hawaii
United States	Straub Pearlridge Clinic	'Aiea	Hawaii
United States	The Cancer Center of Hawaii-Pali Momi	'Aiea	Hawaii
United States	The Queen's Medical Center - West Oahu	'Ewa Beach	Hawaii
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Riverwood Healthcare Center	Aitkin	Minnesota
United States	Lovelace Medical Center-Downtown	Albuquerque	New Mexico
United States	Lovelace Medical Center-Saint Joseph Square	Albuquerque	New Mexico
United States	Lovelace Radiation Oncology	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	OSF Saint Anthony's Health Center	Alton	Illinois
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Anchorage Radiation Therapy Center	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Aspirus Langlade Hospital	Antigo	Wisconsin
United States	Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California
United States	Cone Health Cancer Center at Asheboro	Asheboro	North Carolina
United States	Randolph Hospital	Asheboro	North Carolina
United States	Mission Hospital	Asheville	North Carolina
United States	Duluth Clinic Ashland	Ashland	Wisconsin
United States	Northwest Wisconsin Cancer Center	Ashland	Wisconsin
United States	Carle Cancer Institute Normal	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Rush-Copley Medical Center	Aurora	Illinois
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Northwell Health Imbert Cancer Center	Bay Shore	New York
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Saint Charles Health System	Bend	Oregon
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph's/Candler - Bluffton Campus	Bluffton	South Carolina
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Saint Michael Cancer Center	Bremerton	Washington
United States	IHA Hematology Oncology Consultants-Brighton	Brighton	Michigan
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Minnesota Oncology - Burnsville	Burnsville	Minnesota
United States	Cambridge Medical Center	Cambridge	Minnesota
United States	IHA Hematology Oncology Consultants-Canton	Canton	Michigan
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	AtlantiCare Health Park-Cape May Court House	Cape May Court House	New Jersey
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Caro Cancer Center	Caro	Michigan
United States	Saint Anthony Regional Hospital	Carroll	Iowa
United States	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Saint Luke's Hospital	Cedar Rapids	Iowa
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	Medical University of South Carolina	Charleston	South Carolina
United States	IHA Hematology Oncology Consultants-Chelsea	Chelsea	Michigan
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Hematology Oncology Consultants-Clarkston	Clarkston	Michigan
United States	Newland Medical Associates-Clarkston	Clarkston	Michigan
United States	Wake Forest University at Clemmons	Clemmons	North Carolina
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Saint Francis Cancer Center	Colorado Springs	Colorado
United States	Columbus NCI Community Oncology Research Program	Columbus	Colorado
United States	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Bay Area Hospital	Coos Bay	Oregon
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Greater Regional Medical Center	Creston	Iowa
United States	Carle on Vermilion	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Essentia Health - Deer River Clinic	Deer River	Minnesota
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Porter Adventist Hospital	Denver	Colorado
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Essentia Health Saint Mary's - Detroit Lakes Clinic	Detroit Lakes	Minnesota
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	Columbus Oncology and Hematology Associates	Dublin	Ohio
United States	Dublin Methodist Hospital	Dublin	Ohio
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Northside Hospital - Duluth	Duluth	Georgia
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan
United States	Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	AtlantiCare Surgery Center	Egg Harbor Township	New Jersey
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Medical Center Fargo	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Sanford South University Medical Center	Fargo	North Dakota
United States	Southpointe-Sanford Medical Center Fargo	Fargo	North Dakota
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Saint Francis Hospital	Federal Way	Washington
United States	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota
United States	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan
United States	Genesee Hematology Oncology PC	Flint	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Trinity Regional Medical Center	Fort Dodge	Iowa
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Regional Cancer Center-Lee Memorial Health System	Fort Myers	Florida
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	Essentia Health - Fosston	Fosston	Minnesota
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Central Ohio Breast and Endocrine Surgery	Gahanna	Ohio
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Central Care Cancer Center - Garden City	Garden City	Kansas
United States	Nebraska Cancer Specialists/Oncology Hematology West PC	Grand Island	Nebraska
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	Central Carolina Surgery	Greensboro	North Carolina
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	Novant Health Breast Surgery - Greensboro	Greensboro	North Carolina
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Academic Hematology Oncology Specialists	Grosse Pointe Woods	Michigan
United States	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan
United States	Michigan Breast Specialists-Grosse Pointe Woods	Grosse Pointe Woods	Michigan
United States	Mount Carmel Grove City Hospital	Grove City	Ohio
United States	Lehigh Valley Hospital-Hazelton	Hazleton	Pennsylvania
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Essentia Health Hibbing Clinic	Hibbing	Minnesota
United States	Island Urology-Hilo	Hilo	Hawaii
United States	South Carolina Cancer Specialists PC	Hilton Head Island	South Carolina
United States	The Radiation Oncology Center-Hilton Head/Bluffton	Hilton Head Island	South Carolina
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Hawaii Diagnostic Radiology Services LLC	Honolulu	Hawaii
United States	Island Urology	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Kuakini Medical Center	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	Aspirus Langlade Hospital	Irvine	California
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Essentia Health - Jamestown Clinic	Jamestown	North Dakota
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Straub Medical Center - Kahului Clinic	Kahului	Hawaii
United States	Castle Medical Center	Kailua	Hawaii
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Novant Health Cancer Institute - Kernersville	Kernersville	North Carolina
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Marshfield Clinic - Ladysmith Center	Ladysmith	Wisconsin
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Sparrow Hospital	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Northside Hospital - Gwinnett	Lawrenceville	Georgia
United States	Beebe Medical Center	Lewes	Delaware
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Saint Rita's Medical Center	Lima	Ohio
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Saint Joseph London	London	Kentucky
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Jewish Hospital	Louisville	Kentucky
United States	Saints Mary and Elizabeth Hospital	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Michigan Breast Specialists-Macomb Township	Macomb	Michigan
United States	OhioHealth Mansfield Hospital	Mansfield	Ohio
United States	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	OhioHealth Marion General Hospital	Marion	Ohio
United States	Saint Mary's Oncology/Hematology Associates of Marlette	Marlette	Michigan
United States	Culicchia Neurological Clinic LLC	Marrero	Louisiana
United States	West Jefferson Medical Center	Marrero	Louisiana
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Cone Heath Cancer Center at Mebane	Mebane	North Carolina
United States	Aspirus Medford Hospital	Medford	Wisconsin
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Monticello Cancer Center	Monticello	Minnesota
United States	Novant Health Cancer Institute - Mount Airy	Mount Airy	North Carolina
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Louisiana State University Health Science Center	New Orleans	Louisiana
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	Newark Radiation Oncology	Newark	Ohio
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Lakeland Hospital Niles	Niles	Michigan
United States	Cancer and Hematology Centers of Western Michigan - Norton Shores	Norton Shores	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Ascension Borgess Cancer Center	Oshtemo	Michigan
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Essentia Health - Park Rapids	Park Rapids	Minnesota
United States	Parker Adventist Hospital	Parker	Colorado
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Mercy Health - Perrysburg Hospital	Perrysburg	Ohio
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	21st Century Oncology-Pontiac	Pontiac	Michigan
United States	Hope Cancer Center	Pontiac	Michigan
United States	Newland Medical Associates-Pontiac	Pontiac	Michigan
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Fairview Northland Medical Center	Princeton	Minnesota
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Saint Charles Health System-Redmond	Redmond	Oregon
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Annie Penn Memorial Hospital	Reidsville	North Carolina
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Aspirus Cancer Care - Wisconsin Rapids	Sacramento	California
United States	Aspirus Regional Cancer Center	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Essentia Health Sandstone	Sandstone	Minnesota
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-Cherry Hill	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Providence Regional Cancer System-Shelton	Shelton	Washington
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Suburban Hematology Oncology Associates - Snellville	Snellville	Georgia
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Springfield Memorial Hospital	Springfield	Illinois
United States	Novant Health Cancer Institute - Statesville	Statesville	North Carolina
United States	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan
United States	Marshfield Clinic Stevens Point Center	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri
United States	Ascension Saint Joseph Hospital	Tawas City	Michigan
United States	Sanford Thief River Falls Medical Center	Thief River Falls	Minnesota
United States	Novant Health Cancer Institute - Thomasville	Thomasville	North Carolina
United States	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	Mercy Health - Saint Vincent Hospital	Toledo	Ohio
United States	Mercy Health Sylvania Radiation Oncology Center	Toledo	Ohio
United States	Munson Medical Center	Traverse City	Michigan
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Carle Cancer Center	Urbana	Illinois
United States	Carle Cancer Center NCI Community Oncology Research Program	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Essentia Health Virginia Clinic	Virginia	Minnesota
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Advanced Breast Care Center PLLC	Warren	Michigan
United States	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan
United States	Macomb Hematology Oncology PC	Warren	Michigan
United States	Michigan Breast Specialists-Warren	Warren	Michigan
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	Mercy Hospital Washington	Washington	Missouri
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Novant Health Cancer Institute - Wilkesboro	Wilkesboro	North Carolina
United States	Wake Forest Baptist Health - Wilkes Medical Center	Wilkesboro	North Carolina
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Aspirus Cancer Care - Wisconsin Rapids	Wisconsin Rapids	Wisconsin
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Sanford Cancer Center Worthington	Worthington	Minnesota
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	Fairview Lakes Medical Center	Wyoming	Minnesota
United States	Metro Health Hospital	Wyoming	Michigan
United States	Providence Regional Cancer System-Yelm	Yelm	Washington
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Huron Gastroenterology PC	Ypsilanti	Michigan
United States	IHA Hematology Oncology Consultants-Ann Arbor	Ypsilanti	Michigan
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Guam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline Neurocognitive Function at 10 weeks - Hopkins Verbal Learning Test-Revised (HVLT-R)	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.	Baseline,10 weeks
Primary	Change from Baseline Neurocognitive Function at 10 weeks - Trail Making Test Part A and B (TMT A & B)	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. TMT-B is similar except subjects are required to connect 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 score for TMT-A and TMT-B 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.	Baseline,10 weeks
Primary	Change from Baseline Neurocognitive Function at 10 weeks - Controlled Oral Word Association Test (COWA)	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 (F-A-S). The score on the COWA is the total number of words named across the three trials minus repetitions.	Baseline,10 weeks
Primary	Efficacy of Ramipril of Neurocognitive Function at Baseline - Shipley Institute of Living Scale-Version 2 Vocabulary	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. Score is total correct of 40 items and will be used in conjunction with the other neurocognitive results.	Baseline
Primary	Retention Rate at 10 weeks	Measured by the percent of patients who took 75% of the Ramipril doses and completed the neurocognitive battery of tests	10 weeks
Secondary	Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20)	A 50-item questionnaire with a 20-item brain cancer specific section, used to assess the physical and psychosocial functioning and symptom experience. All of the scales and single-item measures range in score from 0 to 100 with standardization.	Baseline, 6 weeks, 10 weeks, 22 weeks
Secondary	Estimate Time of Neurocognitive Decline- HVLT-R	Measured by the first significant decline of the HVLT-R.	Baseline - 22 weeks
Secondary	Estimate Time of Neurocognitive Decline- TMT A & B	Measured by the first significant decline of the TMT A & B	Baseline - 22 weeks
Secondary	Estimate Time of Neurocognitive Decline- COWA	Measured by the first significant decline of the COWA	Baseline - 22 weeks
Secondary	Determine Presence of Apolipoprotein Epsilon (ApoE)	Measured by quantitative polymerase chain reaction (PCR) using patient serum via a blood test	Baseline
Secondary	Efficacy of neurocognitive function in surviving patients- HVLT-R	Comparison of HVLT-R results between groups at study end.	22 weeks
Secondary	Efficacy of neurocognitive function in surviving patients- TMT A & B	Comparison of TMT A & B results between groups at study end.	22 weeks
Secondary	Efficacy of neurocognitive function in surviving patients- COWA	Comparison of COWA results between groups at study end.	22 weeks
Secondary	Efficacy of neurocognitive function in surviving patients- EORTCQLQ30/BN20	Comparison of EORTCQLQ30/BN20 results between groups at study end.	22 weeks