A Clinical Trial Evaluating the Efficacy of Valganciclovir in Glioblastoma Patients

NCT04116411 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: Eudra CT: 2019-001083-30
• Study Type: interventional
• Target: 220
• Locations: 2 countries
• Sites: 3

Brief Summary

This study is a multicenter randomized double-blinded controlled phase 2 study evaluating the efficacy and safety of the anti-CMV drug valganciclovir vs placebo as add-on therapy in patients with glioblastoma. Valganciclovir is approved for treatment of cytomegalovirus (CMV) infections, but may also have anti-tumoral effects. Current evidence imply that most glioblastomas are CMV positive and that the virus can affect tumor aggressiveness.

Conditions

Glioblastoma Multiforme

Keywords

cytomegalovirus; valganciclovir

Outcome Measures

Primary Outcomes (2)

• Impact of valganciclovir on median overall survival of glioblastoma patients

  Median overall survival will be analyzed using Cox regression analysis and presented by Kaplan-Meier graphs. Proportion of patients alive at 12 or 24 months, respectively, in each study arm and will be analyzed using Fisher exact test.

  Study closure at 30 months follow up. Survival analyses will be analysed at 12 and 24 months.

• Baseline and demographic data

  All baseline and demographic data will be analysed using descriptive statistics such as mean, medians, standard deviations etc. for all variables which are continuous. Variables that are categorical will be analysed using frequency tables with number of patients and percent. All these analyses will be divided by treatment group. No formal hypothesis testing will be performed for the demographic and baseline variables.

  At 30 months follow up

Secondary Outcomes (5)

• Progression free survival at 12 and 24 months

  12 and 24 months

• Incidence of valganciclovir treatment related adverse events

  30 months follow up time

• Health related Quality of Life using EORTC QLQ30 module

  Base line and at every 3 months until 24 months follow up.

• Cognitive functions

  up to 24 months

• Health related Quality of Life using the EORTC BN20 module

  Base line and at every 3 months until 24 months follow up.

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Patients will receive placebo tablets with similar appearance as the active drug. Patients receive two 450 mg tablets twice daily taken per orally for 6 weeks, thereafter two 450 mg tablet once daily for an additional 22.5 months; a total treatment time of 24 months.

Drug: Temozolomide 120 mg; Radiation: Radiotherapy 60 Gy; Drug: Placebo oral tablet

Valganciclovir

ACTIVE COMPARATOR

Patients will receive valganciclovir tablets with similar appearance as the placebo tablets. Patients receive two 450 mg valganciclovir tablets twice daily taken per orally for 6 weeks, thereafter two 450 mg valganciclovir tablets once daily for an additional 22.5 months; a total treatment time of 24 months.

Drug: Valganciclovir Tablets; Drug: Temozolomide 120 mg; Radiation: Radiotherapy 60 Gy

Interventions

Valganciclovir Tablets DRUG

Valganciclovir treatment of glioblastoma

Also known as: Valcyte, ValGANcilovir, Valganciclovir 450 mg, J05AB14, Valganciclovir oral

Valganciclovir

Temozolomide 120 mg DRUG

Chemotherapy

Also known as: Temozolomide pill, Temozolomide tablet

Placebo; Valganciclovir

Radiotherapy 60 Gy RADIATION

Radiation therapy

Also known as: Radiation

Placebo; Valganciclovir

Placebo oral tablet DRUG

Placebo treatment of glioblastoma

Also known as: Placebos

Placebo

Eligibility Criteria

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

You may qualify if:

• Patients aged 18 years or older
• Patients with newly diagnosed glioblastoma, IDH 1 wt, WHO grade IV
• Radical resection
• Concomitant treatment with temozolomide and radiation therapy
• MGMT promoter methylation status
• Patients with at least KPS 70 , ECOG/WHO 2
• Patients providing written informed consent
• Patients cooperative and able to complete all the assessment procedures.
• Females of child-bearing age must have a negative pregnancy test at screening (all premenopausal women, or in case when menstrual status can not be ascertained in women under the age of 55). Female patient must agree to utilize a highly efficient birth control method throughout the study period (Pearl index \<1, e.g: oral contraception with gestagens, transdermal contraceptives, implants, injectables, intrauterine devices, bilateral tubal occlusion, sexual abstinence or vasectomised partner). The birth control method must be used at least 30 days after treatment end. Pregnancy testing should be performed at monthly intervals due to high teratogenic potential of valganciclovir. Men are recommended to use condoms with female partners during, and for at least 90 days following treatment with Valganciclovir.
• Patients must be enrolled within 10 weeks after surgery

You may not qualify if:

• Patients allergic to, or who do not tolerate Valganciclovir, aciclovir or valaciclovir treatment
• Patients with decreased cognitive function (below 24 in MMSE test)
• Pregnant or lactating females
• Patients not signing informed consent
• Patient is simultaneously participating in another experimental drug therapy trial
• Neutrophil count \< 1,5 cells/ 109/L
• Platelet count \< 150 cells/ 109/L
• HGB \< 80 g/L
• Abnormal renal function (GFR \< 30)
• Secondary glioblastoma, or glioblastoma IDH1 mutated.
• Unfit for any other reason judged by investigator

Sponsors & Collaborators

• Cecilia Soderberg-Naucler: lead
• Karolinska University Hospital: collaborator
• Karolinska Institutet: collaborator

Study Sites (3)

Oslo University Hospital

Oslo, Norway

Location

Stavanger University Hospital

Stavanger, Norway

Location

SE01 Karolinska University Hospital

Solna, Stockholm County, SE17164, Sweden

Location

Related Publications (6)

• Peredo I, Hellden A, Wolmer-Solberg N, Pohanka A, Stragliotto G, Rahbar A, Stahle L, Bellander BM, Soderberg-Naucler C. Ganciclovir concentrations in the cerebral extracellular space after valganciclovir treatment; a case study. BMJ Case Rep. 2015 Dec 15;2015:bcr2014207694. doi: 10.1136/bcr-2014-207694.

  PMID: 26670887 BACKGROUND

• Rahbar A, Orrego A, Peredo I, Dzabic M, Wolmer-Solberg N, Straat K, Stragliotto G, Soderberg-Naucler C. Human cytomegalovirus infection levels in glioblastoma multiforme are of prognostic value for survival. J Clin Virol. 2013 May;57(1):36-42. doi: 10.1016/j.jcv.2012.12.018. Epub 2013 Feb 4.

  PMID: 23391370 BACKGROUND

• Cobbs CS. Does valganciclovir have a role in glioblastoma therapy? Neuro Oncol. 2014 Mar;16(3):330-1. doi: 10.1093/neuonc/nou009. No abstract available.

  PMID: 24523453 BACKGROUND

• Stragliotto G, Rahbar A, Solberg NW, Lilja A, Taher C, Orrego A, Bjurman B, Tammik C, Skarman P, Peredo I, Soderberg-Naucler C. Effects of valganciclovir as an add-on therapy in patients with cytomegalovirus-positive glioblastoma: a randomized, double-blind, hypothesis-generating study. Int J Cancer. 2013 Sep 1;133(5):1204-13. doi: 10.1002/ijc.28111. Epub 2013 Mar 13.

  PMID: 23404447 RESULT

• Soderberg-Naucler C, Peredo I, Stragliotto G. Valganciclovir in patients with glioblastoma. N Engl J Med. 2013 Nov 21;369(21):2066-7. doi: 10.1056/NEJMc1312413. No abstract available.

  PMID: 24256396 RESULT

• Merchut-Maya JM, Bartek J Jr, Bartkova J, Galanos P, Pantalone MR, Lee M, Cui HL, Shilling PJ, Brochner CB, Broholm H, Maya-Mendoza A, Soderberg-Naucler C, Bartek J. Human cytomegalovirus hijacks host stress response fueling replication stress and genome instability. Cell Death Differ. 2022 Aug;29(8):1639-1653. doi: 10.1038/s41418-022-00953-w. Epub 2022 Feb 22.

  PMID: 35194187 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

Valganciclovir; Temozolomide; Radiation

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Ganciclovir; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Physical Phenomena

Study Officials

• Giuseppe Stragliotto, MD, PhD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: VIGAS 2 is conducted under a randomised double blinded protocol. The study team and the patients are blinded to the randomisation list. Randomisation is performed by the contracted Clinical Cancer Center Unit at the Karolinska University Hospital by an unblinded person, Claudia Maes who holds responsibility to select out number codes for coded cans of the study drug. Claudia Maes is unrelated to the sponsor and the study team.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: A multicenter randomized double-blinded controlled phase 2 study evaluating the efficacy of valganciclovir as add-on therapy in glioblastoma patients. Patients will receive either placebo or valganciclovir according to a randomisation list, blinded to the sponsor and study team. Seven centers are aimed to include patients once approval is received for each respective study center.

Study Record Dates

• First Submitted: August 29, 2019
• First Posted: October 4, 2019
• Study Start: September 4, 2019
• Primary Completion (Estimated): September 16, 2027
• Study Completion (Estimated): September 16, 2027
• Last Updated: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: When data is available and permissions to share these are approved, data will be available for other researchers.
• Access Criteria: Access will be given by the sponsor upon request.

Locations

SE (1); NO (2)