A Clinical Trial Evaluating the Efficacy of Valganciclovir in Glioblastoma Patients (VIGAS2)

Cecilia Soderberg-Naucler

Status and phase: Active, not recruiting; Phase 2

Conditions: Glioblastoma Multiforme

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

Study type: Interventional

Funder types: Other

Identifiers

NCT04116411

Eudra CT: 2019-001083-30

Details and patient eligibility

About

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.

Full description

Adult patients will either be randomized to standard treatment (temozolomide and radiation therapy) + placebo tablets or to standard treatment + valganciclovir. Patients are randomized using 1 to 1 distribution of the patients between the treatment groups and are stratified according to methylation status of the MGMT promoter; equal proportion of patients are included in each group. A maximum of 30% of patients with methylated MGMT promoter are allowed into the study (to harmonise with current data used for statistical power calculation), as MGMT promotor methylation status is prognostic for patient survival. Patients must enter the study within 10 weeks after surgery.

Full dose treatment with 900mgs of Valganciclovir is given twice daily for 6 weeks, thereafter 900 mgs daily during 98 weeks (total treatment of 24 months). Valganciclovir is available in 450 mg tablets. The dose of Valganciclovir will be adjusted according to renal function.

This study will be performed in compliance with the protocol, ICH-GCP, the declaration of Helsinki and applicable Swedish regulatory requirements.

The study discontinuation criteria are as follows:

• Withdrawal of consent
• An adverse event which requires discontinuation of the trial medication or results in
• inability to continue to comply with trial procedures
• Disease progression which results in inability to continue to comply with trial
• procedures
• Major Protocol deviations
• Exclusion criteria met

Enrollment: 220 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients aged 18 years or older
2. Patients with newly diagnosed glioblastoma, IDH 1 wt, WHO grade IV
3. Radical resection
4. Concomitant treatment with temozolomide and radiation therapy
5. MGMT promoter methylation status
6. Patients with at least KPS 70 , ECOG/WHO 2
7. Patients providing written informed consent
8. Patients cooperative and able to complete all the assessment procedures.
9. 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.
10. Patients must be enrolled within 10 weeks after surgery

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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220 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Radiation: Radiotherapy 60 Gy

Drug: Temozolomide 120 mg

Drug: Placebo oral tablet

Valganciclovir

Active Comparator group

Description:

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.

Treatment:

Radiation: Radiotherapy 60 Gy

Drug: Temozolomide 120 mg

Drug: Valganciclovir Tablets