Memantine +/- Raloxifene for Cognitive Preservation After Radiation Therapy to the Brain (MemoryRT)

Memory RT: Memantine +/- Raloxifene for Cognitive Preservation After Radiation Therapy to the Brain

The study investigators are testing to see if patients receiving radiation treatment for brain cancer along with raloxifene plus memantidine take longer to develop memory issues.

The study will include anyone over the age of 18 who will be treated with radiation for brain cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Brain Tumor
• Intervention / Treatment: Drug: Memantine; Drug: Raloxifene

Detailed Description

As cognitive decline is a common side effect after external beam radiation therapy to the brain, estrogen receptor beta (ERβ) modulation presents an unexploited target for mitigating this adverse effect as well.

The investigators seek to address two scientific questions to improve quality of life in patients and improve cancer outcomes: 1) can estrogen modulation further augment neuroprotection achieved by memantine after radiation therapy to the brain? and 2) can estrogen modulation lead to measurable tumor control improvement and molecular changes in CNS malignancies?

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Andrew J Brenner, MD, PhD; Phone Number: 210-562-4090; Email: brennera@uthscsa.edu
• Study Contact Backup: Name: Eva M Galvan, MD; Phone Number: 210-450-1093; Email: GalvanE@uthscsa.edu

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Mays Cancer Center, UT Health San Antonio
      • Contact: Kayla Chamberlain; Phone Number: 210-450-5964; Email: chamberlink@uthscsa.edu
      • Principal Investigator: Andrew J Brenner, MD, PhD
      • Principal Investigator: Eva M Galvan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years.
2. Ability to provide informed written consent in either English or Spanish.
3. All individuals of childbearing potential must have a negative serum pregnancy test and male and female subjects must agree to use effective means of contraception (surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an Intrauterine device (IUD)) with their partner from entry into the study through 24 weeks after the last dose of Raloxifene.
4. Patients undergoing radiation therapy to the brain as a part of solid tumor cancer therapy, using intensity modulated radiation therapy (IMRT) or whole brain radiation therapy (WBRT).Willingness to adhere to planned study drug regimen, including obtaining medication from an outside pharmacy via prescription.
5. Patients must have a creatinine clearance ≥ 50 mL/min (using Cockcroft-Gault Equation).
6. Patients must not have hepatic impairment greater than Child-Pugh Score "Class A".

Exclusion Criteria:

1. History of prior radiotherapy to the brain.
2. Life expectancy of < 6 months.
3. Radiation Therapy planned is ≤ 5 fractions (e.g.stereotactic radiosurgery (SRS)or Steriotactic radiotherapy (SRT), or 5-fraction whole brain).
4. Contraindications to taking memantine and/or raloxifene based on package inserts and the clinical judgement of the treating physician .
5. The subject is unable to undergo magnetic resonance imaging (MRI) scan (e.g., has an MRI incompatible pacemaker).
6. Conditions or situations which, in the opinion of the investigator, imply the patient will be unable or not suitable to complete trial requirements or at excessive risk from trial participation.
7. Known allergy to either of the medications (Memantine or Raloxifene) used in this study or their excipients.
8. Cognitive failure as assessed by Mini Mental State Exam (MMSE) score <17

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A: Standard of Care; Patients will start Memantine as SOC around the time of radiation. Memantine may be continued as SOC as prescribed by the treating physician after the 24 weeks.	Drug: Memantine; The goal dose for Immediate Release Memantine is 10 mg oral twice daily. The goal-dose for Extended-Release Memantine is 21 mg daily.; Other Names: Namenda
Experimental: Group B: Standard of Care plus raloxifene; Patients will start Memantine as SOC around the time of radiation. Memantine may be continued as SOC as prescribed by the treating physician after the 24 weeks. If randomized to group B patients will be recommended to start the assigned Raloxifene at least one week before their anticipated RT treatment start date.	Drug: Memantine; The goal dose for Immediate Release Memantine is 10 mg oral twice daily. The goal-dose for Extended-Release Memantine is 21 mg daily.; Other Names: Namenda; Drug: Raloxifene; Raloxifene will be administered at 120mg orally every day; Other Names: Evista

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hippocampal volume changes	MRIs will be used to capture any changes in hippocampal volume	Baseline to 48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eastern Cooperative Oncology Group Performance Status score	A 0-5 scale to assess a cancer patient's functional ability showing how their daily life is impacted by the disease. A score of 0 means fully active, while a higher score indicates increasing disability with 5 indicating death.	Baseline to study termination visit (approximately 48 weeks)
Hopkins Verbal Learning Test Revised (HLVT-R) Score	HVLT-R scoring involves summing words recalled in learning trials for Total Recall, calculating Percentage Retention (Delayed Recall / Higher of Trials 2/3), and determining the Recognition Discrimination Index (True Positives - False Positives). These raw scores are then converted to age-adjusted T-scores, which are compared to normative data (16-92 years old) to assess verbal learning and memory in brain-disordered populations, with higher scores generally indicating better performance.	Week 0 to study termination visit (approximately 48 weeks)
Trail Making Test -A (TMT-A) Score	A neuropsychological number test measuring psychomotor speed and visual attention by connecting numbers (1-25) in sequence. Higher scores (more time) indicate greater impairment, with averages around 29 seconds, while scores over 30-40 seconds often suggest potential cognitive issues, though norms vary by age and education.	Week 0 to study termination visit (approximately 48 weeks)
Trail Making Test -B (TMT-B) Score	A neuropsychological number and letter test measuring psychomotor speed and visual attention by connecting numbers (1-25) in sequence. Higher scores (more time) indicate greater impairment, with averages around 75 seconds, while scores over 273 second often suggest potential cognitive issues, though norms vary by age and education.	Week 0 to study termination visit (approximately 48 weeks)
Controlled Oral Word Association (COWA) Test Score	A neuropsychological test assessing verbal fluency and executive functions like self-initiation, requiring a person to name as many words as possible starting with a specific letter (like F, A, S, or C, F, L) within 60 seconds, for three trials, while avoiding repetitions, proper nouns, or variations of the same word root to gauge cognitive health, especially after brain injury or with conditions like dementia. The score includes the total number of unique, correct words across the trials. A higher score indicated better cognitive function.	Week 0 to study termination visit (approximately 48 weeks)
European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Brain (BN)tumor-20	A 20 item questionnaire with each item scored from 0-4 with a total possible score of 0-80. A higher score indicates a worse quality of life.	Week 0 to study termination visit (approximately 48 weeks)
MD Anderson Symptom Inventory Brain Tumor (MDASI-BT)	Involves rating 23 symptoms and 6 interference items on a 0-10 scale (0=not present/did not interfere, 10=as bad as you can imagine/interfered completely) for the last 24 hours, calculating mean scores for overall symptoms, symptom factors (like neurological, cognitive, GI), and interference (activity/mood), with scores of 5 or greater indicating moderate-to-severe symptoms. Scores are averaged for summary measures, providing a picture of symptom burden and its impact on daily life for brain tumor patients. A mean of the total score is calculated with a higher score indicating worse symptoms.	Week 0 to study termination visit (approximately 48 weeks)
Functional Assessment of Cancer Therapy - Brain (FACT-Br)	A total of 50 items are included that cover the following domains of Quality of life (QOL): physical well-being, social/family well-being, emotional well-being, functional well-being, and disease specific concerns. Patients are asked to indicate the presence/severity of certain issues/symptoms on a scale of 0 - 4 (a 5-point Likert Scale).The range of scores is 0-148 with a higher indicating a better quality of life.	Week 0 to study termination visit (approximately 48 weeks)
Medical Outcomes Study - Cognitive Function (MOS-CF)	The Medical Outcomes Study Cognitive Functioning Scale is a patient-reported measure of perceived cognitive functioning consisting of six items that assess the frequency of problems with concentration, reasoning, confusion, forgetfulness, and mental clarity during the previous four weeks. Each item is scored on a 6-point Likert scale ranging from 1 ("all of the time") to 6 ("none of the time"), where higher values indicate fewer cognitive difficulties. Item scores are summed to generate a raw total score ranging from 6 to 36, with higher scores reflecting better cognitive functioning and fewer reported cognitive problems, and lower scores indicating greater perceived impairment. In some studies the raw score is also linearly transformed to a 0-100 scale, where 0 represents the worst cognitive functioning and 100 represents the best cognitive functioning.	Week 0 to study termination visit (approximately 48 weeks)
Patient Reported Outcomes Measurement Information System - Cognitive Function (PROMIS-CF)	The PROMIS-CF score is derived from two items: (1) My memory has been as good as usual and (2) I have been able to focus my attention, which ask patients to self-report on their cognitive abilities with the following response scale: 1 = Not at all, 2 = A little bit, 3 = Somewhat; 4 = Quite a bit, and 5 = Very much. Total scores are from 1-10 with a higher score indicating better cognitive function.	Week 0 to study termination visit (approximately 48 weeks)
Hopkins Verbal Learning Test Revised HLVT-R DR	Hopkins Verbal Learning Test-Revised Delayed Recall is a neuropsychological test assessing verbal memory by having individuals recall a list of 12 words after a delay (around 20-25 minutes). Scoring is from 0-12 with a higher score indicating better recall.	Week 0 to study termination visit (approximately 48 weeks)
Hopkins Verbal Learning Test Revised HLVT-R RECOG	The Hopkins Verbal Learning Test-Revised recognition discrimination index is a component of the HVLT-R that evaluates verbal recognition memory following presentation of a 12-word learning list. After the delayed recall phase, participants complete a recognition trial consisting of 24 items (the 12 original target words mixed with 12 distractor words). For each item, the respondent indicates whether the word was part of the original list (yes/no). Scoring is based on the Recognition Discrimination Index (RDI), calculated as the number of correct recognitions (hits) minus the number of incorrect endorsements of distractors (false positives). The resulting score ranges from -12 to +12, with higher scores indicating better recognition memory and greater ability to discriminate target words from distractors, while lower scores reflect poorer recognition performance and greater memory impairment.	Week 0 to study termination visit (approximately 48 weeks)

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2031

Study Registration Dates

• First Submitted: March 9, 2026
• First Submitted That Met QC Criteria: March 9, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Radiation therapy; Intensity modulated radiation therapy (IMRT); Solid tumor cancer
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Benzene Derivatives; Adamantane; Bridged-Ring Compounds; Stilbenes; Benzylidene Compounds; Amantadine; Tamoxifen; Memantine; Raloxifene Hydrochloride
• Other Study ID Numbers: CTMS# 25-0146

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data may be shared with groups involved in overseeing this research study including monitors, data safety monitoring committee, any law enforcement agencies, the IRB or any state or local health departments. Any de-identified results will be submitted for publication in a peer reviewed journal.
• IPD Sharing Time Frame: IPD will be shared at study completion after the data analysis is complete and the publication is accepted in a peer review journal
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• 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