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

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).

Timeline

Start

2026-05

Primary completion

2028-05

Completion

2030-05

Publications

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• Background Shireman JM, White Q, Agrawal N, et al. Genomic Analysis of Human Brain Metastases Treated with Stereotactic Radiosurgery Under the Phase-II Clinical Trial (NCT03398694) Reveals DNA Damage Repair at the Peripheral Tumor Edge. medRxiv [Preprint]. 2023 Apr 24:2023.04.15.23288491. doi: 10.1101/2023.04.15.23288491. PMID: 37131583; PMCID: PMC10153341
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• Background Corroyer-Dulmont A, Valable S, Fantin J, Chatre L, Toutain J, Teulier S, Bazille C, Letissier E, Levallet J, Divoux D, Ibazizene M, Guillouet S, Perrio C, Barre L, Serres S, Sibson NR, Chapon F, Levallet G, Bernaudin M. Multimodal evaluation of hypoxia in brain metastases of lung cancer and interest of hypoxia image-guided radiotherapy. Sci Rep. 2021 May 27;11(1):11239. doi: 10.1038/s41598-021-90662-0.
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• Background Voloshin T, Kaynan N, Davidi S, Porat Y, Shteingauz A, Schneiderman RS, Zeevi E, Munster M, Blat R, Tempel Brami C, Cahal S, Itzhaki A, Giladi M, Kirson ED, Weinberg U, Kinzel A, Palti Y. Tumor-treating fields (TTFields) induce immunogenic cell death resulting in enhanced antitumor efficacy when combined with anti-PD-1 therapy. Cancer Immunol Immunother. 2020 Jul;69(7):1191-1204. doi: 10.1007/s00262-020-02534-7. Epub 2020 Mar 6.
• Background Kissling C, Di Santo S. Tumor Treating Fields - Behind and Beyond Inhibiting the Cancer Cell Cycle. CNS Neurol Disord Drug Targets. 2020;19(8):599-610. doi: 10.2174/1871527319666200702144749.
• Background Kim EH, Jo Y, Sai S, Park MJ, Kim JY, Kim JS, Lee YJ, Cho JM, Kwak SY, Baek JH, Jeong YK, Song JY, Yoon M, Hwang SG. Tumor-treating fields induce autophagy by blocking the Akt2/miR29b axis in glioblastoma cells. Oncogene. 2019 Sep;38(39):6630-6646. doi: 10.1038/s41388-019-0882-7. Epub 2019 Aug 2.
• Background 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.
• Background Chen H, Liu R, Liu J, Tang J. Growth inhibition of malignant melanoma by intermediate frequency alternating electric fields, and the underlying mechanisms. J Int Med Res. 2012;40(1):85-94. doi: 10.1177/147323001204000109.
• Background 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.
• Background Mehta MP et al. Results from METIS (EF-25), an international, multicenter phase III randomized study evaluating the efficacy and safety of tumor treating fields (TTFields) therapy in NSCLC patients with brain metastases. JCO. 2024; 42, 2008-2008.DOI:10.1200/JCO.2024.42.16_suppl.2008
• Background Bokstein F, Blumenthal D, Limon D, Harosh CB, Ram Z, Grossman R. Concurrent Tumor Treating Fields (TTFields) and Radiation Therapy for Newly Diagnosed Glioblastoma: A Prospective Safety and Feasibility Study. Front Oncol. 2020 Apr 21;10:411. doi: 10.3389/fonc.2020.00411. eCollection 2020.
• Background Lu G, Rao M, Zhu P, Liang B, El-Nazer RT, Fonkem E, Bhattacharjee MB, Zhu JJ. Triple-drug Therapy With Bevacizumab, Irinotecan, and Temozolomide Plus Tumor Treating Fields for Recurrent Glioblastoma: A Retrospective Study. Front Neurol. 2019 Jan 31;10:42. doi: 10.3389/fneur.2019.00042. eCollection 2019.
• Background 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.
• 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

Drugs

Indications