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

Official title

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

Overview

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.

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?

Interventions

• 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.
• Drug Raloxifene
  Raloxifene will be administered at 120mg orally every day

Primary outcome measures

• Hippocampal volume changes [Time frame: Baseline to 48 weeks]

Secondary outcome measures (12)

• Eastern Cooperative Oncology Group Performance Status score [Time frame: Baseline to study termination visit (approximately 48 weeks)]
• Hopkins Verbal Learning Test Revised (HLVT-R) Score [Time frame: Week 0 to study termination visit (approximately 48 weeks)]
• Trail Making Test -A (TMT-A) Score [Time frame: Week 0 to study termination visit (approximately 48 weeks)]
• Trail Making Test -B (TMT-B) Score [Time frame: Week 0 to study termination visit (approximately 48 weeks)]
• Controlled Oral Word Association (COWA) Test Score [Time frame: 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 [Time frame: Week 0 to study termination visit (approximately 48 weeks)]
• MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) [Time frame: Week 0 to study termination visit (approximately 48 weeks)]
• Functional Assessment of Cancer Therapy - Brain (FACT-Br) [Time frame: Week 0 to study termination visit (approximately 48 weeks)]
• Medical Outcomes Study - Cognitive Function (MOS-CF) [Time frame: Week 0 to study termination visit (approximately 48 weeks)]
• Patient Reported Outcomes Measurement Information System - Cognitive Function (PROMIS-CF) [Time frame: Week 0 to study termination visit (approximately 48 weeks)]
• Hopkins Verbal Learning Test Revised HLVT-R DR [Time frame: Week 0 to study termination visit (approximately 48 weeks)]
• Hopkins Verbal Learning Test Revised HLVT-R RECOG [Time frame: Week 0 to study termination visit (approximately 48 weeks)]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years.
• Ability to provide informed written consent in either English or Spanish.
• 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.
• 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.
• Patients must have a creatinine clearance ≥ 50 mL/min (using Cockcroft-Gault Equation).
• Patients must not have hepatic impairment greater than Child-Pugh Score "Class A".

Exclusion criteria

• History of prior radiotherapy to the brain.
• Life expectancy of < 6 months.
• Radiation Therapy planned is ≤ 5 fractions (e.g.stereotactic radiosurgery (SRS)or Steriotactic radiotherapy (SRT), or 5-fraction whole brain).
• Contraindications to taking memantine and/or raloxifene based on package inserts and the clinical judgement of the treating physician .
• The subject is unable to undergo magnetic resonance imaging (MRI) scan (e.g., has an MRI incompatible pacemaker).
• 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.
• Known allergy to either of the medications (Memantine or Raloxifene) used in this study or their excipients.
• Cognitive failure as assessed by Mini Mental State Exam (MMSE) score <17

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Mays Cancer Center, UT Health San Antonio — San Antonio

Identifiers

NCT: NCT07470606 · CTMS# 25-0146

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗