A Study in Subjects With Recurrent Malignant Glioma
- Registration Number
- NCT01137604
- Lead Sponsor
- Eisai Inc.
- Brief Summary
An open-label phase 2, multicenter study in participants with recurrent malignant glioma.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 151
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1 Lenvatinib Cohort 1 assessed participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive. Participants were planned to be accrued in Cohort 1 and randomized in a 1:1 ratio to receive lenvatinib (experimental) or bevacizumab (active comparator). Cohort 1 - Bevacizumab Cohort 1 - Lenvatinib Cohort 1 Bevacizumab Cohort 1 assessed participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive. Participants were planned to be accrued in Cohort 1 and randomized in a 1:1 ratio to receive lenvatinib (experimental) or bevacizumab (active comparator). Cohort 1 - Bevacizumab Cohort 1 - Lenvatinib Cohort 2 Lenvatinib Cohort 2 assessed participants with recurrent Grade 3 malignant glioma who were bevacizumab-naive. Participants in Cohort 2 were planned to be treated with lenvatinib. Cohort 3 Lenvatinib Cohort 3 assessed participants with recurrent GBM who had disease progression following prior bevacizumab treatment. Participants in Cohort 3 were planned to be treated with lenvatinib.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) Rate at Month 6 At Month 6 from randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) PFS at Month 6 was defined as the percentage of participants who remained alive and progression-free at Month 6, based on investigator's assessment. Progression was defined using Response Assessment in Neuro-Oncology (RANO) criteria, as a greater than 25% increase in enhancing lesions despite stable or increasing steroid dose, an increase (significant) in non-enhancing T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) lesions that are not attributable to other non-tumor causes, and any new lesions. PFS rate at Month 6 was estimated from Kaplan-Meier (K-M) product-limit estimate of PFS.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until disease progression, development of unacceptable toxicity, withdrawal of consent or up to data cutoff date of 19 March 2013 (i.e., 2.4 years) ORR was the percentage of participants with best overall response (BOR) of complete response (CR) and partial response (PR) based on RANO criteria and investigator's assessment. CR was defined as the disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks, no new lesions, and stable or improved non-enhancing (T2/FLAIR) lesions. PR was defined as greater than or equal to 50% decrease, compared to baseline, in the sum of products of perpendicular diameters of all measureable enhancing lesions sustained for at least 4 weeks. No progression of non-measurable disease, no new lesions, stable or improved non-enhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared to baseline. For both CR and PR, in the absence of a confirming scan 4 weeks later, this scan was considered only stable disease. Only participants with measureable disease at baseline were included in evaluation of ORR.
Progression Free Survival From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until disease progression, development of unacceptable toxicity, withdrawal of consent or up to data cutoff date of 19 March 2013 (ie, 2.4 years) PFS was measured as the time from randomization (Cohort 1) or the first day of treatment (Cohorts 2 and 3) until the date of first documentation of disease progression or date of death, if death occurred prior to disease progression, based on investigator's assessment.
Overall Survival (OS) From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until death due to any cause or up to data cutoff date of 19 March 2013 (ie, 2.4 years) OS was measured as the time from the randomization date (Cohort 1) or the first day of treatment (Cohort 2 and 3) to the date of death from any cause.
Disease Control Rate (DCR) From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until disease progression, development of unacceptable toxicity, withdrawal of consent or up to data cutoff date of 19 March 2013 (ie, 2.4 years) DCR was the percentage of the participants who had BOR of CR, PR, and stable disease (SD) with the minimum duration of SD lasting greater than or equal to 7 weeks. Only participants with measurable disease at baseline were included in evaluation of DCR, based on investigator's assessment.
Clinical Benefit Rate (CBR) From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until disease progression, development of unacceptable toxicity, withdrawal of consent or up to data cutoff date of 19 March 2013 (ie, 2.4 years) CBR was the percentage of the participants who had BOR of CR, PR, and SD with the minimum duration of SD lasting greater than or equal to 23 weeks. Only participants with measurable disease at baseline were included in evaluation of CBR, based on investigator's assessment.
Number of Participants With Adverse Events (AEs)/Serious Adverse Events (SAEs) as a Measure of Safety For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) Safety was assessed by monitoring and recording all AEs including all Common Terminology Criteria for Adverse Events (CTCAE) grades (for both increasing and decreasing severity) and SAEs; regular monitoring of hematology, clinical chemistry, and urine values; results of physical examinations, regular measurement of vital signs, and electrocardiograms (ECGs), as detailed in the Schedule of Visits and Procedures. The relationship of AEs to treatment was based on investigator judgment. Details of AEs and SAEs are provided in the reported adverse event section.