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Testing Ramipril to Prevent Memory Loss in People With Glioblastoma

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ClinicalTrials.gov Identifier: NCT03475186
Recruitment Status : Recruiting
First Posted : March 23, 2018
Last Update Posted : March 4, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Tracking Information
First Submitted Date  ICMJE March 2, 2018
First Posted Date  ICMJE March 23, 2018
Last Update Posted Date March 4, 2021
Actual Study Start Date  ICMJE March 25, 2019
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 24, 2018)
  • Change from Baseline Neurocognitive Function at 10 weeks - Hopkins Verbal Learning Test-Revised (HVLT-R) [ Time Frame: 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.
  • Change from Baseline Neurocognitive Function at 10 weeks - Trail Making Test Part A and B (TMT A & B) [ Time Frame: 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. 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.
  • Change from Baseline Neurocognitive Function at 10 weeks - Controlled Oral Word Association Test (COWA) [ Time Frame: 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 (F-A-S). The score on the COWA is the total number of words named across the three trials minus repetitions.
  • Efficacy of Ramipril of Neurocognitive Function at Baseline - Shipley Institute of Living Scale-Version 2 Vocabulary [ Time Frame: Baseline ]
    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.
  • Retention Rate at 10 weeks [ Time Frame: 10 weeks ]
    Measured by the percent of patients who took 75% of the Ramipril doses and completed the neurocognitive battery of tests
Original Primary Outcome Measures  ICMJE
 (submitted: March 21, 2018)
  • Change from Baseline Neurocognitive Function at 10 weeks - Hopkins Verbal Learning Test-Revised (HVLT-R) [ Time Frame: 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.
  • Change from Baseline Neurocognitive Function at 10 weeks - Trail Making Test Part A and B (TMT A & B) [ Time Frame: 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. 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.
  • Change from Baseline Neurocognitive Function at 10 weeks - Controlled Oral Word Association Test (COWA) [ Time Frame: 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 (F-A-S). The score on the COWA is the total number of words named across the three trials minus repetitions.
  • Efficacy of Ramipril of Neurocognitive Function at 10 weeks - Shipley Institute of Living Scale-Version 2 Vocabulary [ Time Frame: Baseline ]
    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.
  • Retention Rate at 10 weeks [ Time Frame: 10 weeks ]
    Measured by the percent of patients who took 75% of the Ramipril doses and completed the neurocognitive battery of tests
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2018)
  • Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) [ Time Frame: Baseline, 6 weeks, 10 weeks, 22 weeks ]
    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.
  • Estimate Time of Neurocognitive Decline- HVLT-R [ Time Frame: Baseline - 22 weeks ]
    Measured by the first significant decline of the HVLT-R.
  • Estimate Time of Neurocognitive Decline- TMT A & B [ Time Frame: Baseline - 22 weeks ]
    Measured by the first significant decline of the TMT A & B
  • Estimate Time of Neurocognitive Decline- COWA [ Time Frame: Baseline - 22 weeks ]
    Measured by the first significant decline of the COWA
  • Determine Presence of Apolipoprotein Epsilon (ApoE) [ Time Frame: Baseline ]
    Measured by quantitative polymerase chain reaction (PCR) using patient serum via a blood test
  • Efficacy of neurocognitive function in surviving patients- HVLT-R [ Time Frame: 22 weeks ]
    Comparison of HVLT-R results between groups at study end.
  • Efficacy of neurocognitive function in surviving patients- TMT A & B [ Time Frame: 22 weeks ]
    Comparison of TMT A & B results between groups at study end.
  • Efficacy of neurocognitive function in surviving patients- COWA [ Time Frame: 22 weeks ]
    Comparison of COWA results between groups at study end.
  • Efficacy of neurocognitive function in surviving patients- EORTCQLQ30/BN20 [ Time Frame: 22 weeks ]
    Comparison of EORTCQLQ30/BN20 results between groups at study end.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2018)
  • Efficacy of Ramipril on Non-Memory Cognitive Functions- M.D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) [ Time Frame: Baseline, 6 weeks, 10 weeks, 22 weeks, 34 weeks, 46 weeks, 58 weeks ]
    A 28-item questionnaire to assess the severity of 13 symptom items and 6 interference items, as well as, 9 symptoms specific to brain tumors at their worst in the last 24 hours on a 0-10 scale, with 0 being "not present" and 10 being "as bad as you can imagine."
  • Efficacy of Ramipril on Non-Memory Cognitive Functions-EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTCQLQ30/BN20) [ Time Frame: Baseline, 6 weeks, 10 weeks, 22 weeks, 34 weeks, 46 weeks, 58 weeks ]
    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.
  • Estimate Time of Neurocognitive Decline- HVLT-R [ Time Frame: Baseline - 58 weeks ]
    Measured by the first significant decline of the HVLT-R.
  • Estimate Time of Neurocognitive Decline- TMT A & B [ Time Frame: Baseline - 58 weeks ]
    Measured by the first significant decline of the TMT A & B
  • Estimate Time of Neurocognitive Decline- COWA [ Time Frame: Baseline - 58 weeks ]
    Measured by the first significant decline of the COWA
  • Determine Presence of Apolipoprotein Epsilon (ApoE) [ Time Frame: Baseline ]
    Measured by quantitative polymerase chain reaction (PCR) using patient serum via a blood test
  • Efficacy of neurocognitive function in surviving patients- HVLT-R [ Time Frame: 58 weeks ]
    Comparison of HVLT-R results between groups at study end.
  • Efficacy of neurocognitive function in surviving patients- TMT A & B [ Time Frame: 58 weeks ]
    Comparison of TMT A & B results between groups at study end.
  • Efficacy of neurocognitive function in surviving patients- COWA [ Time Frame: 58 weeks ]
    Comparison of COWA results between groups at study end.
  • Efficacy of neurocognitive function in surviving patients- MDASI-BT [ Time Frame: 58 weeks ]
    Comparison of MDASI-BT results between groups at study end.
  • Efficacy of neurocognitive function in surviving patients- EORTCQLQ30/BN20 [ Time Frame: 58 weeks ]
    Comparison of EORTCQLQ30/BN20 results between groups at study end.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Testing Ramipril to Prevent Memory Loss in People With Glioblastoma
Official Title  ICMJE A Single Arm, Pilot Study of Ramipril for Preventing Radiation-Induced Cognitive Decline in Glioblastoma (GBM) Patients Receiving Brain Radiotherapy
Brief 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.
Detailed 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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Glioblastoma
  • Radiotherapy; Complications
  • Cognitive Decline
  • Chemoradiation
Intervention  ICMJE Drug: Ramipril
2.5 - 5 mg oral, 1x daily for 22 weeks
Other Names:
  • Altace
  • Tritace
Study Arms  ICMJE Experimental: 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).
Intervention: Drug: Ramipril
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 21, 2018)
75
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2021
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 ≤ 35 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. 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.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Karen Craver, MT, MHA 336-716-0891 NCORP@wakehealth.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03475186
Other Study ID Numbers  ICMJE IRB00053531
3UG1CA189824-04S1 ( U.S. NIH Grant/Contract )
NCI-2018-01807 ( Registry Identifier: NCI CTRP )
WF-1801 ( Other Identifier: Wake Forest NCORP Research Base )
NCI-2018-01807 ( Registry Identifier: NCI CTRP (Clinical Trial Reporting Program) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Wake Forest NCORP Research Base is committed to following the NIH Statement on Sharing Research Data (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html). As of July 2018, the WF NCORP RB signed an agreement with NCI to contribute de-identified data and data dictionaries from clinical trials conducted through our RB to the NCI NCTN/NCORP data archive within 6 months of primary and non-primary publications of phase II/III and phase III trials to https://nctn-data-archive.nci.nih.gov/. This will become the primary means for sharing raw data, and we will adhere to the guidelines spelled out in the NCTN/NCORP Data Archive Usage Guide. De-identified data from studies not covered by the agreement (e.g., phase II and observational studies) will be made available upon request. All data files will be de-identified. De-identification procedures will meet the HIPAA criteria as detailed in the Code of Federal Regulations, Part 45, Section 164.514.
Time Frame: 6 months after publication for a 2 year duration
Access Criteria: upon request to NCORP@wakehealth.edu
Responsible Party Wake Forest University Health Sciences
Study Sponsor  ICMJE Wake Forest University Health Sciences
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Michael D Chan, MD Wake Forest University Health Sciences
PRS Account Wake Forest University Health Sciences
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP