Trial to Study Anti- HCMV Therapy in Breast Cancer Patients With Progressive Intracranial Metastases and CMV Infection

NCT07383649 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: Pro00040888 (HMCC-BR25-001)
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Brain Cancer Metastatic; CMV Viremia

Outcome Measures

Primary Outcomes (1)

• 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.

  6 Weeks

Secondary Outcomes (10)

• Safety and toxicity of anti- HCMV therapy (Valganciclovir) as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTAE) v5

  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

  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

  104 Weeks

• Prevention of memory decline with anti-HCMV therapy (Valganciclovir) and SOC prevention of memory decline with anti-HCMV therapy (Valganciclovir) and SOC

  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.

  104 Weeks

Other Outcomes (1)

• Exploratory Outcome

  104 Weeks

Study Arms (1)

Anti-HCMV therapy (Oral Valganciclovir) and Standard-of-Care

EXPERIMENTAL

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

Interventions

Valganciclovir DRUG

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

Anti-HCMV therapy (Oral Valganciclovir) and Standard-of-Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged \>18 years at the time of consent
• Breast cancer with progressive brain metastases supra and/or infratentorial. 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 one non irradiated, untreated progressive brain metastases site
• Serum HCMV DNA by real time PCR \> 250 copies/ml or positive CMV Ig G or Ig M.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol. If the patient is unable to consent for any reason a legally authorized guardian may provide consent on their behalf. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act) will be obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
• Metastatic breast cancer who has systemically no evidence of disease, complete remission, partial remission, stable or progressive disease
• Eastern Cooperative Oncology Group (ECOG) performance score of 0-2
• Adequate hematology without ongoing transfusion support (hemoglobin \> 9 g/dl, absolute neutrophil count (ANC) \> 1500 per mm3 , platelets \> 100,000 per mm3)
• Adequate renal and hepatic function (creatinine clearance \[CrCL\] \> 60 mL/min, bilirubin x:≤1.5 upper limit of normal (ULN), aspartate aminotransferase \[AST\] and alanine aminotransferase \[ALT\] ≤ 2.5 x ULN and serum albumin ≥ 3 g/dl.
• Other CMV treatment if clinically indicated per physician's choice
• 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:
• Women \<50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the postmenopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
• Women ≥50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow-up.

You may not qualify if:

• Single resectable intracranial lesion
• Last intracranial progression free survival \> 12 months
• All progressive brain metastases have been radiated
• Brain metastases needing immediate local intervention such as mass effect, herniation, active neurological symptoms, increased intracranial pressure, those near vital structures like the motor cortex, proximity to the optic nerve/chiasm or brain stem etc (can still be included if there are any other non-radiated progressive brain metastases) Multidisciplinary discussion with neurosurgery and radiation oncology will be needed to determine which patients may be safely enrolled on the trial.
• Active pregnancy or breast feeding
• Women of childbearing potential or fertile men unwilling to use effective contraception (Section 6.2, Table 6) during study and up to three months after treatment discontinuation.
• Known psychiatric disorder that causes poor cooperation with the trial requirements.
• Participants with previous other malignancies must have had at least a 3-year disease free interval, except those with non-melanoma skin cancer or carcinoma in situ of cervix
• Participation in another clinical study with an investigational product within 28 days prior to the first dose of study treatment.
• Concurrent enrollment in another clinical study unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Unresolved or unstable adverse events (AEs) from prior administration of another investigational drug, per investigators' discretion.
• Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of study treatment.
• Non-English-speaking subjects will not be enrolled in this study since the neurocognitive tests including DKEFS, RAVLT and TMT are not validated to be scored in other languages.

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead

Study Sites (1)

Houston Methodist Neal Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (17)

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  PMID: 20181476 BACKGROUND

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  PMID: 8433390 BACKGROUND

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  BACKGROUND

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• Chen D, Le SB, Hutchinson TE, Calinescu AA, Sebastian M, Jin D, Liu T, Ghiaseddin A, Rahman M, Tran DD. Tumor Treating Fields dually activate STING and AIM2 inflammasomes to induce adjuvant immunity in glioblastoma. J Clin Invest. 2022 Apr 15;132(8):e149258. doi: 10.1172/JCI149258.

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• Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, Di Meco F, Lieberman F, Zhu JJ, Stragliotto G, Tran D, Brem S, Hottinger A, Kirson ED, Lavy-Shahaf G, Weinberg U, Kim CY, Paek SH, Nicholas G, Bruna J, Hirte H, Weller M, Palti Y, Hegi ME, Ram Z. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017 Dec 19;318(23):2306-2316. doi: 10.1001/jama.2017.18718.

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  BACKGROUND

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• Meletath SK, Pavlick D, Brennan T, Hamilton R, Chmielecki J, Elvin JA, Palma N, Ross JS, Miller VA, Stephens PJ, Snipes G, Rajaram V, Ali SM, Melguizo-Gavilanes I. Personalized Treatment for a Patient With a BRAF V600E Mutation Using Dabrafenib and a Tumor Treatment Fields Device in a High-Grade Glioma Arising From Ganglioglioma. J Natl Compr Canc Netw. 2016 Nov;14(11):1345-1350. doi: 10.6004/jnccn.2016.0145.

  PMID: 27799506 BACKGROUND

• Tran DD et al. Final analysis of 2-THE-TOP: A phase 2 study of TTFields (Optune) plus pembrolizumab plus maintenance temozolomide (TMZ) in patients with newly diagnosed glioblastoma. JCO. 2023; 41, 2024-2024.DOI:10.1200/JCO.2023.41.16_suppl.2024

  BACKGROUND

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Valganciclovir

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Ganciclovir; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Akshjot Puri, M.D.

  The Houston Methodist Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Milan Sheth

CONTACT

346-238-7169; mksheth2@houstonmethodist.org

Titilayo Olubajo

CONTACT

713-363-9803; tolubajo@houstonmethodist.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2026
• First Posted: February 3, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2030
• Last Updated: April 8, 2026

Record last verified: 2026-04

Locations

US (1)