Bevacizumab Alone Versus Dose-dense Temozolomide Followed by Bevacizumab for Recurrent Glioblastoma, Phase III (RE-GEND)
|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: NCT02761070|
Recruitment Status : Recruiting
First Posted : May 4, 2016
Last Update Posted : February 27, 2019
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Recurrence Progression||Drug: Temozolomide Drug: Bevacizumab||Phase 3|
Glioblastoma (GBM), the most frequent malignant primary brain tumor, has yet been incurable despite recent progress on its standard of care using TMZ as the main trunk of initial therapy in the newly diagnosed setting. One of the main reasons accounting for the dismal prognosis would attribute to lack of active therapeutic regimens at recurrence.
Bevacizumab, a humanized monoclonal antibody against cardinal angiogenic factor vascular endothelial growth factor (VEGF), has recently shown efficacy for recurrent GBM, and has been approved in Japan, thereby being a standard care for recurrent GBM. Since there is no effective drugs or regimens developed at bevacizumab failure, insertion of another active drug prior to bevacizumab induction would enhance survival time for patients with recurrent GBM.
In Japan, there are currently only few chemotherapeutic agents approved and available for GBM. Among them rechallenge with alternating dosing of TMZ have shown certain efficacy with acceptable toxicities for patients with TMZ-pretreated recurrent GBM, thus being a good candidate for the regimen used prior to bevacizumab at recurrence.
The present proposal of sequential administration of dose dense TMZ (7/14d) followed by bevacizumab wishes to define a new standard of care for recurrent disease and hopes to identify the subgroups of patients with progressive or recurrent glioblastoma that respond particularly well to dose-dense temozolomide regimens.
This study is carried out as a JCOG Brain Tumor Study Group multicenter randomized phase III trial under approval by Advanced Medical Care B system, Ministry of Health, Labour and Welfare, Japan.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||210 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter Randomized Phase III Study for Recurrent Glioblastoma Comparing Bevacizumab Alone With Dose-dense Temozolomide Followed by Bevacizumab (JCOG1308C, RE-GEND-pIII)|
|Study Start Date :||July 11, 2016|
|Estimated Primary Completion Date :||July 10, 2022|
|Estimated Study Completion Date :||July 10, 2023|
Active Comparator: Bevacizumab (BEV) alone
Bevacizumab 10 mg/kg, day 1 div, every 2 weeks
Other Name: Avastin
Experimental: Dose Dense Temozolomide Followed by BEV
Temozolomide (120 mg/m2, po, 7 days on/7 days off, every 2 weeks per cycle) up to 48 cycles. The dose will be escalated to 150 mg/m2 at 3rd cycle if the defined conditions are met throughout the first 2 cycles. At recurrence or progression, bevacizumab alone(10 mg/kg, day 1 div, every 2 weeks)
Other Name: Avastin
- Overall survival [ Time Frame: Time to event. Up to 2 years from the last patient in. ]Overall survival will be measured from registration until death for any reason. If the patient is alive at last follow-up, the patient will be censored at the last time of confirmation of survival.
- Progression-free survival (PFS) [ Time Frame: Time to event. Up to 2 years from the last patient in. ]Progression free will be measured from registration until the first occurrence of progression or death.
- 6-month progression-free survival (6m-PFS) [ Time Frame: 6 months from registration ]Number of patients without progression at 6 months from registration divided by number of all registered
- Complete response rate [ Time Frame: Through study completion, an average of 1 year ]Complete response rate is defined as the rate of complete response after chemotherapy in cases with measurable lesions through completion/termination of the protocol treatment.
- Response rate [ Time Frame: Through study completion, an average of 1 year ]Response rate is defined as the rate of complete response/partial response after chemotherapy in cases with measurable lesions through completion/termination of the protocol treatment.
- Adverse events [ Time Frame: Up to 1 year after completion/termination of the protocol treatment. ]Each adverse event must be graded as the worst grade observed during the entire treatment period of each treatment protocol according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) up to 1 year.
- Serious adverse events [ Time Frame: Up to 1 year after completion/termination of the protocol treatment. ]Each serious adverse event must be recorded according to CTCAE v4.0 up to 1 year.
- Progression-free survival (PFS) from bevacizumab (BEV) initiation [ Time Frame: Time to event from initiation of BEV. Up to 2 years from the last patient in. ]Progression free from BEV initiation will be measured from the day of initiation of BEV until the first occurrence of progression or death.
- 6-month progression-free survival (6m-PFS) after initiation of bevacizumab (BEV) (Experimental Arm Only) [ Time Frame: 6 months from initiation of BEV ]Number of patients without progression at 6 months from the day of initiation of BEV divided by number of all second-line (BEV) treated in Experimental Arm
- Overall survival after initiation of bevacizumab (BEV) [ Time Frame: Time to event from initiation of BEV. Up to 2 years from the last patient in. ]Overall survival from the day of initiation of BEV until death for any reason. If the patient is alive at last follow-up, the patient will be censored at the last time of confirmation of survival.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02761070
|Contact: Motoo Nagane, M.D., Ph.D.||+81-422-47-5511 ext firstname.lastname@example.org|
|Contact: Keiichi Kobayashi, M.D., Ph.D.||+81-422-47-5511 ext email@example.com|
|Study Chair:||Motoo Nagane, M.D., Ph.D.||Kyorin University Faculty of Medicine, Department of Neurosurgery|