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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04116411
Recruitment Status : Recruiting
First Posted : October 4, 2019
Last Update Posted : October 4, 2019
Sponsor:
Collaborators:
Karolinska University Hospital
Karolinska Institutet
Information provided by (Responsible Party):
Cecilia Soderberg-Naucler, Karolinska Institutet

Tracking Information
First Submitted Date  ICMJE August 29, 2019
First Posted Date  ICMJE October 4, 2019
Last Update Posted Date October 4, 2019
Actual Study Start Date  ICMJE September 4, 2019
Estimated Primary Completion Date August 31, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 3, 2019)
  • Impact of valganciclovir on median overall survival of glioblastoma patients [ Time Frame: Study closure at 30 months follow up. Survival analyses will be analysed at 12 and 24 months. ]
    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.
  • Baseline and demographic data [ Time Frame: At 30 months follow up ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: October 3, 2019)
  • Progression free survival at 12 and 24 months [ Time Frame: 12 and 24 months ]
    Tumor recurrence is estimated as clinical and radiological determination (RANO criteria and NANO criteria). The progression free survival will be calculated as the (date of progression - date of first dose of study drug). Patients who are alive without progression at end of follow-up will be censored. Patients who are withdrawn from the study during the follow-up for other reason than dead will be censored at time of withdrawal. Patients who dies for any reason during the follow-up without any progression will be classified as progression using date of death as date of progression. Patients are analysed for stable disease, surgical interventions and treatment failure. Progression free survival will be analysed using Cox regression analysis and presented by Kaplan-Meier graphs. The difference in 12 and 24 months progression free survival rates for patients treated with valganciclovir or placebo will be analysed using Fisher exact test.
  • Incidence of valganciclovir treatment related adverse events [ Time Frame: 30 months follow up time ]
    Number of patients with treatment related adverse events, as assessed by CTCv4. Vital signs: blood pressure (mmHg), heart rate (beats per minute), temperature (degree Celsius), clinical laboratory (total blood counts and differential analyses, liver transaminases and bilirubin, and renal function (creatinine and GFR) and physical exam. Adverse events will be analyzed using a chi-square test without continuity correction.
  • Health related Quality of Life using EORTC QLQ30 module [ Time Frame: Base line and at every 3 months until 24 months follow up. ]
    Quality of Life measures are recoreded according to EORTC QLQ30 and BN20 module, that are validated for brain tumor patients and measured as a unit of scale. There will be a comparison of scores for patients receiving valganciclovir versus placebo treatment. These are standard tools for assessing patients reported quality of Life along time during treatment. The change from baseline will be analysed using Wilcoxon Rank Sum test.
  • Cognitive functions [ Time Frame: up to 24 months ]
    MMSE (Mini Mental State Examination) tests are made with a questionary form and will be assesses every three months during the study. The change from baseline will be analysed using Wilcoxon Rank Sum test.
  • Health related Quality of Life using the EORTC BN20 module [ Time Frame: Base line and at every 3 months until 24 months follow up. ]
    Quality of Life measures are recoreded according to BN20 module, that are validated for brain tumor patients and measured as a unit of scale. There will be a comparison of scores for patients receiving valganciclovir versus placebo treatment. These are standard tools for assessing patients reported quality of Life along time during treatment. The change from baseline will be analysed using Wilcoxon Rank Sum test.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Clinical Trial Evaluating the Efficacy of Valganciclovir in Glioblastoma Patients
Official Title  ICMJE A Multicenter Randomized Double-blinded Controlled Phase 2 Study Evaluating the Efficacy of Valganciclovir as add-on Therapy in Glioblastoma Patients
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.
Detailed 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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
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.
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma Multiforme
Intervention  ICMJE
  • Drug: Valganciclovir Tablets
    Valganciclovir treatment of glioblastoma
    Other Names:
    • Valcyte
    • ValGANcilovir
    • Valganciclovir 450 mg
    • J05AB14
    • Valganciclovir oral
  • Drug: Temozolomide 120 mg
    Chemotherapy
    Other Names:
    • Temozolomide pill
    • Temozolomide tablet
  • Radiation: Radiotherapy 60 Gy
    Radiation therapy
    Other Name: Radiation
  • Drug: Placebo oral tablet
    Placebo treatment of glioblastoma
    Other Name: Placebos
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    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 one 450 mg tablet twice daily for an additional 22.5 months; a total treatment time of 24 months.
    Interventions:
    • Drug: Temozolomide 120 mg
    • Radiation: Radiotherapy 60 Gy
    • Drug: Placebo oral tablet
  • Active Comparator: Valganciclovir
    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 one 450 mg valganciclovir tablet twice daily for an additional 22.5 months; a total treatment time of 24 months.
    Interventions:
    • Drug: Valganciclovir Tablets
    • Drug: Temozolomide 120 mg
    • Radiation: Radiotherapy 60 Gy
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 3, 2019)
220
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 31, 2024
Estimated Primary Completion Date August 31, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Cecilia Soderberg-Naucler, MD, PhD +46702427471 cecilia.naucler@ki.se
Contact: Afsar Rahbar, PhD +46769496980 afsar.rahbar@ki.se
Listed Location Countries  ICMJE Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04116411
Other Study ID Numbers  ICMJE Eudra CT: 2019-001083-30
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: When approval from authorities in Sweden allows data sharing, these will be available for other researchers.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: 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.
Responsible Party Cecilia Soderberg-Naucler, Karolinska Institutet
Study Sponsor  ICMJE Cecilia Soderberg-Naucler
Collaborators  ICMJE
  • Karolinska University Hospital
  • Karolinska Institutet
Investigators  ICMJE
Principal Investigator: Giuseppe Stragliotto, MD, PhD Karolinska University Hospital
PRS Account Karolinska Institutet
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP