A Multicenter Randomized Double-blinded Controlled Phase 2 Study Evaluating the Efficacy of Valganciclovir as add-on Therapy in Glioblastoma Patients
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 220
- 试验地点
- 3
- 主要终点
- Impact of valganciclovir on median overall survival of glioblastoma patients
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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 two 450 mg tablet once daily for an additional 22.5 months; a total treatment time of 24 months.
干预措施: Temozolomide 120 mg (Drug)
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 two 450 mg tablet once daily for an additional 22.5 months; a total treatment time of 24 months.
干预措施: Radiotherapy 60 Gy (Radiation)
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 two 450 mg tablet once daily for an additional 22.5 months; a total treatment time of 24 months.
干预措施: Placebo oral tablet (Drug)
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 two 450 mg valganciclovir tablets once daily for an additional 22.5 months; a total treatment time of 24 months.
干预措施: Valganciclovir Tablets (Drug)
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 two 450 mg valganciclovir tablets once daily for an additional 22.5 months; a total treatment time of 24 months.
干预措施: Temozolomide 120 mg (Drug)
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 two 450 mg valganciclovir tablets once daily for an additional 22.5 months; a total treatment time of 24 months.
干预措施: Radiotherapy 60 Gy (Radiation)
结局指标
主要结局
Impact of valganciclovir on median overall survival of glioblastoma patients
时间窗: 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
时间窗: 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.
次要结局
- 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 the EORTC BN20 module(Base line and at every 3 months until 24 months follow up.)
- 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)
研究者
Cecilia Soderberg-Naucler
Professor
Karolinska Institutet