Phase 2 Multicenter Randomized Double-Blind Controlled Study on Valganciclovir Efficacy in Newly Diagnosed Glioblastoma Patients

The primary objective of this study is to compare the **median overall survival (OS)** time in patients with newly-diagnosed glioblastoma, specifically those with less than 1 cm³ of remaining contrast-enhancing tumor postoperatively. The comparison is between patients treated with and without **valganciclovir** as an add-on to standard therapy. The primary endpoint is the median OS at the end of the study, defined as the time from resection until death from any cause. This objective is clinically relevant as it aims to determine the potential benefit of valganciclovir in extending survival in glioblastoma patients, a condition known for its poor prognosis.

The secondary objectives include:

• Comparing different survival and toxicity parameters in patients treated with and without valganciclovir.
• Evaluating one-year (12 months) and two-year (24 months) survival rates.
• Assessing median progression-free survival (PFS) time, defined as the time from resection to disease progression or death.
• Conducting quality of life assessments using EORTC QLQ C30 and BN20 questionnaires at various intervals up to 30 months.
• Determining the proportion of patients with progressive and stable disease at 12 and 24 months.
• Performing subgroup analyses based on CMV status, Optune treatment, and surgical interventions, focusing on median OS, survival rates, and PFS time.
• Evaluating the safety and tolerance of valganciclovir as an add-on to standard therapy.

The clinical trial involves participants diagnosed with **glioblastoma** WHO grade IV. The study population includes both male and female subjects aged 18 years or older. Participants are required to have undergone a radical tumor resection with no more than 1 cm³ of remaining contrast-enhancing tumor, as assessed by postoperative MRI or CT. The trial does not involve a vulnerable population. Participants must be eligible for standard treatment with radiation therapy combined with concomitant and adjuvant temozolomide. The trial population was selected based on specific inclusion criteria, including a Karnofsky Performance Status (KPS) of 70 or higher and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or lower. Additionally, participants must have a known tumor MGMT promoter methylation status and provide written informed consent. Females of child-bearing potential are required to have a negative pregnancy test at screening and agree to use a highly efficient birth control method throughout the study period and for six months after the last dose of the study drug. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is a **randomized**, **double-blind**, controlled phase 2 study designed to evaluate the efficacy of **valganciclovir** as an add-on therapy in patients with newly diagnosed **glioblastoma**. The primary objective is to compare the median overall survival (OS) time in patients treated with and without valganciclovir in addition to standard therapy. The trial is expected to conclude when the last patient has reached 30 months, with the OS time measured from the time of resection until death from any cause. The study is anticipated to run until December 31, 2027, with recruitment having commenced on September 4, 2019.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, tumor resection status, and ability to undergo standard treatment. Following the screening, participants will be randomized to receive either valganciclovir or a placebo, both administered orally. The study includes regular follow-up visits to monitor survival and toxicity parameters, with the end-of-study visit marking the conclusion of the participant's involvement. The expected duration of participant involvement is up to 30 months, contingent upon individual survival and study completion timelines.

Participants may be subject to early termination from the study under certain conditions, such as withdrawal of consent, significant protocol deviations, or adverse events that compromise safety. The trial's design ensures that all participants receive standard therapy, with the addition of either valganciclovir or placebo, to rigorously assess the impact of the investigational drug on survival outcomes in glioblastoma patients. The study's methodology and procedures are structured to maintain scientific rigor and ensure the collection of reliable data to evaluate the trial's primary and secondary endpoints.

The clinical trial involves the administration of **Valganciclovir**, an anti-viral medication used to treat cytomegalovirus infections. The pharmaceutical form of Valganciclovir is identified as PHF00169MIG, and it is administered orally. The maximum daily dose is 900 mg, with a total maximum dose of 346,500 mg over a treatment period of up to 104 weeks. The active substance, Valganciclovir, is of chemical origin and is classified under the ATC code J05AB14. The trial aims to evaluate the efficacy of Valganciclovir as an add-on therapy in patients with newly-diagnosed glioblastoma.

In addition to the experimental treatment, a **placebo** is used as a comparator in the study. The placebo tablets are manufactured to visually match the Valganciclovir tablets, containing the same excipients but lacking the active compound. The placebo is also administered orally, maintaining the same dosing schedule as the Valganciclovir to ensure blinding in the study. The use of a placebo allows for a controlled comparison to assess the true efficacy of the Valganciclovir treatment.

Efficacy in this clinical trial will be assessed by evaluating the **median overall survival (OS)** time in patients with newly-diagnosed glioblastoma. The primary endpoint is the median OS at the End of Study (EoS), which is defined as the point when the last patient has reached 30 months. OS time is measured from the time of resection until death for any reason. This endpoint will be used to compare patients treated with and without **valganciclovir** as an add-on to standard therapy.

Secondary endpoints include the comparison of different survival and toxicity parameters in the same patient population. The trial is designed as a multicenter, randomized, double-blinded, controlled phase 2 study. The efficacy parameters will be collected and analyzed at the end of the study period, ensuring a comprehensive evaluation of the treatment's impact on survival outcomes.