A Phase 2 interventional study of Valganciclovir in Brain Cancer Metastatic and CMV Viremia, sponsored by The Methodist Hospital Research Institute. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-10.
Sponsored by The Methodist Hospital Research Institute · Phase 2, Interventional, and Treatment
This is a phase II trial with an initial safety lead-in evaluating the efficacy, safety, neurocognitive, and quality-of-life outcomes of anti-cytomegalovirus (CMV) therapy and standard-of-care (SOC) in patients with anti-human cytomegalovirus (HCMV)-reactivated brain metastases. Male and female patients, aged ≥18 years, who have metastatic breast cancer with progressive brain metastases and CMV viremia (> 250 copies/ml) or positive CMV IgG or IgM will be eligible to participate in the trial.
Patients can proceed with SRS as long as at least 1 lesion which is 2 cm or less in a noncritical area in the brain is spared as per the discretion of treating neurosurgeon/radiation oncologist. At least 10 patients will be enrolled in the initial safety lead-in followed by the Phase II trial which will include 18 patients.
Anti-HCMV therapy, oral Valganciclovir will be given to patients at 900 mg twice a day for 2 weeks. After the induction period, the maintenance will be continued with valganciclovir at 450 mg twice daily for 4 weeks (28 days).
This is a phase II trial with an initial safety lead-in evaluating the efficacy, safety, neurocognitive, and quality-of-life outcomes of anti-cytomegalovirus (CMV) therapy and standard-of-care (SOC) in patients with anti-human cytomegalovirus (HCMV)-reactivated brain metastases. Male and female patients, aged ≥18 years, who have metastatic breast cancer with progressive brain metastases and CMV viremia (> 250 copies/ml) or positive CMV IgG or IgM will be eligible to participate in the trial. Patients can proceed with SRS as long as at least 1 lesion which is 2 cm or less in a noncritical area in the brain is spared as per the discretion of treating neurosurgeon/radiation oncologist. Multidisciplinary discussion with neurosurgery and radiation oncology will be needed to determine which patients may be safely enrolled on the trial. At least 10 patients will be enrolled in the initial safety lead-in followed by the Phase II trial which will include 18 patients. The primary endpoint will be to determine the objective response rate after the start of the treatment (anti-HCMV therapy and SOC). Anti-HCMV therapy, oral Valganciclovir will be given to patients at 900 mg twice a day for 2 weeks. Patients will be followed with weekly labs for viral clearance, hematological toxicity, and electrolyte imbalances. CMV PCR, IgG and IgM will be checked at the end of two weeks to monitor for viral clearance. After the induction period, the maintenance will be continued with valganciclovir at 450 mg twice daily for 4 weeks (28 days). Patients will be followed with every 2 weekly labs for hematological toxicity, and electrolyte imbalances. CMV PCR, IgG and IgM will be checked at the end of these four weeks. Pill counting will be done at each follow up to ensure compliance with oral valganciclovir. Patients will be followed with physical examinations and assessment of laboratory parameters as required per standard-of-care treatment. Quality-of-life, neurocognitive questionnaires, and MRI brain (if asymptomatic) every 2 months until subsequent intracranial progression or end of study, whichever comes first. MRI brain will be performed at any symptom onset regardless of study schedule. All MRIs will be evaluated for tumor response and progression using RANO-BM for intracranial and extracranial response using RECIST V1.1.
Patients will be followed for 24 months. Adverse events will be recorded for up to 2 months after treatment discontinuation according to (NCI CTAE) v5. After end of study patients will be followed for survival only.
Correlative studies will include HCMV-DNA copies in serum, and whole-blood based immunophenotyping from baseline to end of anti-CMV treatment. Any craniotomy brain metastatic tissue sample or lumbar puncture done as part of standard of care treatment will also be used for correlative studies. Exploratory blood samples will be transported to Dr Hong Zhao's lab at Fondren building floor 6 in \< 4 hours at Room Temperature (RT, 18-25°C) post-collection. Freeze the stabilized blood at -80 °C. The samples will be thawed and lysed using the SmartTube lysis protocol before adding to MDIPA tubes for analysis. Specimens will be stored for up to 3 years after collection. Specimen samples will be accessed by Dr. Hong Zhao's lab for analysis.
Written informed consent is required before performing any trial-specific tests or procedures. Signing of the informed consent form can occur outside the 28-day screening period. All screening evaluations must be completed and reviewed to confirm that patients meet all eligibility criteria before trial entry. Results of standard-of-care tests or examinations performed prior to obtaining informed consent and within 7-28 days prior to trial entry (except where otherwise specified) may be used for screening assessments rather than repeating such tests. The investigator or qualified designer will maintain a screening log to record details of all patients screened and to confirm eligibility or record reasons for screening failure, as applicable.
Neurocognitive testing will consist of the Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test (TMT), and Delis-Kaplan Executive Function System (DKEFS) letter fluency test at baseline and every 8 weeks until end of study or until subsequent intracranial progression, whichever comes first These tests were selected based on the recommendation of the International Cognition and Cancer Task Force (ICCTF). Testing will require approximately 1 hour to complete and will be conducted by the research assistant.
1,960 studies on the registry are indexed under Brain Neoplasms; 516 are open to participants now.
This study's planned enrollment of 28 is below the median of 40 across 1,458 interventional studies indexed under Brain Neoplasms.
Browse Brain Neoplasms studies →The Methodist Hospital Research Institute is the lead sponsor of 157 studies on the registry; 60 are open to participants now.
Of its 25 completed or terminated interventional studies of FDA-regulated products, 15 (60%) have results posted.
Counted across the registry records on this site, refreshed daily.
Evidence of postmenopausal status or negative serum pregnancy test for premenopausal female patients. Negative serum β-human chorionic gonadotropin pregnancy test within 7 days prior to the first dose of study treatment for premenopausal patients. Women will be considered postmenopausal if they have been amenorrheic for 12 months without an alternative medical cause.
The following age-specific requirements apply:
Exclusion Criteria:
At least 10 patients will be enrolled in the initial safety lead-in followed by the Phase II trial which will include 18 patients. Anti-HCMV therapy, oral Valganciclovir will be given to patients at 900 mg twice a day for 2 weeks. After the induction period, the maintenance will be continued with valganciclovir at 450 mg twice daily for 4 weeks (28 days). CMV PCR, IgG and IgM will be checked at the end of these four weeks. Patients will be followed with physical examinations and assessment of laboratory parameters as required per standard-of-care treatment. Quality-of-life, neurocognitive questionnaires, and MRI brain (if asymptomatic) every 2 months until subsequent intracranial progression or end of study, whichever comes first. Patients will be in follow-up for 24 months.
Drug: Valganciclovir
Valganciclovir inhibits viral DNA polymerase, effectively controlling HCMV reactivation and its associated immunosuppressive effects. Dosing for oral Valganciclovir will be based on standard of care dosing as per FDA in patients with HCMV infection. Dose adjustments will be made by the principal investigator for renal function, treatment-related AEs and disease progression according to the manufacturer's recommendations as they are present in individuals and will be assessed on a case-by-case basis.
Also known as: Valcyte
Objective Response Rate with anti-HMCV Therapy and SOC
To estimate the CNS objective response rate (RANO-BM and RECIST V1.1) with anti-HCMV therapy and standard-of-care in metastatic breast cancer patients with progressive brain metastases and CMV viremia or positive CMV IgG or IgM.
Time frame: 6 Weeks
Safety and toxicity of anti- HCMV therapy (Valganciclovir) as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTAE) v5
To assess the safety and toxicity of anti- HCMV therapy (Valganciclovir) in patients with progressive brain metastases and CMV viremia or positive CMV IgG or Ig M, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTAE) v5.
Time frame: 16 Weeks
Benefit in median overall survival from start of treatment (anti-HCMV therapy and SOC) until the end of follow up after 24 months or death
To estimate the benefit in median overall survival from start of treatment (anti-HCMV therapy and SOC) until the end of follow up after 24 months or death in patients with treated progressive brain metastases and CMV viremia or positive CMV IgG or IgM.
Time frame: 104 Weeks
Prevention of memory decline with anti-HCMV therapy (Valganciclovir) as measured by the mean change in the immediate score on the Rey's Auditory Verbal Learning Test (RAVLT) from baseline to end of study
To estimate the prevention of memory decline with anti-HCMV therapy (Valganciclovir) and SOC in patients with progressive brain metastases and CMV viremia or positive CMV IgG or IgM, as measured by the mean change in the immediate score on the Rey's Auditory Verbal Learning Test (RAVLT) from baseline to end of study
Time frame: 104 Weeks
Prevention of memory decline with anti-HCMV therapy (Valganciclovir) and SOC prevention of memory decline with anti-HCMV therapy (Valganciclovir) and SOC
To estimate the prevention of memory decline with anti-HCMV therapy (Valganciclovir) and SOC in patients with progressive brain metastases and CMV viremia or positive CMV IgG or IgM, as measured by the mean change in percent forgetting score on the Rey's Auditory Verbal Learning Test (RAVLT) from baseline to end of study
Time frame: 104 Weeks
Prevention of memory decline with anti-HCMV therapy (Valganciclovir) and SOC as measured by the mean change in executive function as measured by Trail Making Test (TMT) from baseline to end of study.
To estimate the prevention of memory decline with anti-HCMV therapy (Valganciclovir) and SOC in patients with progressive brain metastases and CMV viremia or positive CMV IgG or IgM, as measured by the mean change in executive function as measured by Trail Making Test (TMT) from baseline to end of study.
Time frame: 104 Weeks
Prevention of memory decline with anti-HCMV therapy (Valganciclovir) and SOC as measured by the mean change in Delis Kaplan Executive Function (DKEFS) Letter Fluency Test from baseline to end of study.
To estimate the prevention of memory decline with anti-HCMV therapy (Valganciclovir) and SOC in patients with progressive brain metastases and CMV viremia or positive CMV IgG or IgM, as measured by the mean change in Delis Kaplan Executive Function (DKEFS) Letter Fluency Test from baseline to end of study.
Time frame: 104 Weeks
prevention of quality-of-life decline with anti-HCMV therapy (Valganciclovir) and SOC as measured by the mean change in EORTC QLQ -C30 questionnaire with brain specific module (BN-20) from baseline to end of study.
To estimate the prevention of quality-of-life decline with anti-HCMV therapy (Valganciclovir) and SOC in patients with progressive brain metastases and CMV viremia or positive CMV IgG or IgM, as measured by the mean change in EORTC QLQ -C30 questionnaire with brain specific module (BN-20) from baseline to end of study.
Time frame: 104 Weeks
Benefit in post stereotactic radiation progression free survival, defined as time from start of treatment (anti-HCMV therapy and SOC) to subsequent intracranial progression in local radiated site or distant site in the brain
To estimate the benefit in post stereotactic radiation progression free survival, defined as time from start of treatment (anti-HCMV therapy and SOC) to subsequent intracranial progression in local radiated site or distant site in the brain in patients with progressive brain metastases and CMV viremia or positive CMV IgG or IgM.
Time frame: 104 Weeks
Median time to distant progression, defined as time from start of treatment (anti-HCMV therapy and SOC) to first sign of distant progression
To determine the median time to distant progression, defined as time from start of treatment (anti-HCMV therapy and SOC) to first sign of distant progression in patients with progressive brain metastases and CMV viremia or positive CMV IgG or IgM.
Time frame: 104 Weeks
Systemic objective response rate with anti-HCMV therapy and SOC
To determine the systemic objective response rate with anti-HCMV therapy and SOC in patients with progressive brain metastases and CMV viremia or positive CMV IgG or IgM
Time frame: 6 Weeks
Exploratory Outcome
To evaluate the blood-based correlates of response to anti-HCMV therapy (Valganciclovir) in patients with progressive brain metastases and CMV viremia or positive CMV IgG or IgM. Blood-based correlates of response will include but are not limited to HCMV-DNA copies, and whole-blood based immunophenotyping
Time frame: 104 Weeks
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