GliomaPhase 2NCT01137604
A Study in Subjects With Recurrent Malignant Glioma
A Phase 2 study testing Lenvatinib and Bevacizumab in people with Glioma, run by Eisai Inc. at 5 sites in 2 countries.
Trial summary
An open-label phase 2, multicenter study in participants with recurrent malignant glioma. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Glioma
- What is being tested?
- Lenvatinib and Bevacizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 151 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 9 Nov 2010to 28 Oct 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed diagnosis of Grade 3 or 4 malignant glioma.
- All subjects who have a first or second recurrence following primary management with surgical resection or biopsy, radiotherapy and up to 2 prior systemic treatments with addition of:
- No prior bevacizumab treatment is allowed for Cohort 1 and Cohort 2.
- Subjects must have disease progression following prior bevacizumab treatment for Cohort 3.
- For all cohorts, no prior anti-vascular endothelial growth factor (VEGF/VEGFR) therapy except for bevacizumab as specified above.
- Karnofsky score of 70% or greater.
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- Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Screening Visit.
- Adequate renal function, adequate bone marrow function, adequate blood coagulation function and adequate liver function, as defined in protocol.
- No evidence of hemorrhage on the baseline magnetic resonance imaging (MRI) scan other than in those subjects who are stable grade 1.
Who cannot join
- Females who are pregnant or breastfeeding.
- Subjects who received enzyme-inducing anti-epileptic agents within 14 days before the first dose of study drug (eg, carbamazepine, phenytoin, phenobarbital, primidone, or oxcarbazepine).
- Active infection requiring intravenous antibiotics.
- Therapeutic anti-coagulation with warfarin, aspirin, nonsteroidal anti-inflammatory drugs or clopidogrel (low molecular weight heparin is acceptable).
- Subjects with 24-hour urine protein greater than or equal to 1 gm.
- Prior surgical resection within 4 weeks, or prior stereotactic biopsy within 2 weeks, of Screening Visit.
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- Prior radiotherapy within 12 weeks unless there is a new area of enhancement consistent with recurrent tumor outside of the radiation field, or there is biopsy-proven unequivocal viable tumor on histopathologic sampling.
- Prior chemotherapy (6 weeks for nitrosoureas), or any investigational agent within 4 weeks unless the subject has recovered from all anticipated toxicities associated with that therapy; prior bevacizumab therapy (Cohorts 1 and 2); for Cohort 3, prior bevacizumab therapy within 3 weeks.
- Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II ; unstable angina; myocardial infarction or stroke within 6 months of the first dose of study drug; or cardiac arrhythmia requiring medical treatment.
- Prolongation of QTc interval to greater than 480 msec.
- Active hemoptysis (bright red blood of at least 1/2 teaspoon) within 3 weeks prior to the first dose of study drug.
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States3 sites
Study site
Boston, Massachusetts
Study site
Durham, North Carolina
Study site
Tampa, Florida
About this study
Official title: An Open-Label, Three-Cohort, Phase 2 Study of E7080 (Lenvatinib) in Subjects With Recurrent Malignant Glioma
An open-label phase 2, multicenter study in participants with recurrent malignant glioma.
- Conditions
- Glioma
- Being tested
- Lenvatinib, Bevacizumab
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenvatinibDrug
Also called E7080
24 mg lenvatinib capsules orally, once daily continuously in 28-day cycles until disease progression, development of unacceptable toxicity or withdrawal of consent.
BevacizumabDrug
Bevacizumab 10 mg/kg administered intravenously every 2 weeks in 28-day cycles until disease progression, development of unacceptable toxicity or withdrawal of consent.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 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 Receives: Drug: Lenvatinib; Drug: Bevacizumab |
| Cohort 2 | Experimental | 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. Receives: Drug: Lenvatinib |
| Cohort 3 | Experimental | 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. Receives: Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS) Rate at Month 6
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.
Measured: At Month 6 from randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3)
Secondary outcomes (6)
Objective Response Rate (ORR)
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.
Measured: 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)
Progression Free Survival
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.
Measured: 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)
Overall Survival (OS)
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.
Measured: 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)
Disease Control Rate (DCR)
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.
Measured: 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)
Clinical Benefit Rate (CBR)
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.
Measured: 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)
Number of Participants With Adverse Events (AEs)/Serious Adverse Events (SAEs) as a Measure of Safety
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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2010 (estimated)
- Study start9 Nov 2010
- Primary completion19 Mar 2013
- Study completion28 Oct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GliomaStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 151 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Eisai Medical Services, Study director, Eisai Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01137604
- Sponsor's protocol ID
- E7080-G000-203
- Status last verified
- May 2016
- First submitted
- 2 Jun 2010
- Last updated
- 29 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Three-Cohort, Phase 2 Study of E7080 (Lenvatinib) in Subjects With Recurrent Malignant Glioma
- ClinicalTrials.gov ID
- NCT01137604
- Acronym / sponsor ID
- E7080-G000-203
- Conditions
- Glioma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 151 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Study start
- 9 Nov 2010 (actual)
- Primary completion
- 19 Mar 2013 (actual)
- Study completion
- 28 Oct 2014 (actual)
- First posted
- 4 Jun 2010 (estimated)
- Results
- Posted 23 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An open-label phase 2, multicenter study in participants with recurrent malignant glioma.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: Lenvatinib, Drug: BevacizumabCohort 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 | Experimental | Drug: LenvatinibCohort 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 | Experimental | Drug: LenvatinibCohort 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. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically confirmed diagnosis of Grade 3 or 4 malignant glioma.
- All subjects who have a first or second recurrence following primary management with surgical resection or biopsy, radiotherapy and up to 2 prior systemic treatments with addition of:
- Karnofsky score of 70% or greater.
- Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Screening Visit.
- Adequate renal function, adequate bone marrow function, adequate blood coagulation function and adequate liver function, as defined in protocol.
Key exclusion criteria (11 listed)
- Females who are pregnant or breastfeeding.
- Subjects who received enzyme-inducing anti-epileptic agents within 14 days before the first dose of study drug (eg, carbamazepine, phenytoin, phenobarbital, primidone, or oxcarbazepine).
- Active infection requiring intravenous antibiotics.
- Therapeutic anti-coagulation with warfarin, aspirin, nonsteroidal anti-inflammatory drugs or clopidogrel (low molecular weight heparin is acceptable).
- Subjects with 24-hour urine protein greater than or equal to 1 gm.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LenvatinibAlso: E708024 mg lenvatinib capsules orally, once daily continuously in 28-day cycles until disease progression, development of unacceptable toxicity or withdrawal of consent. | Drug | Cohort 1, Cohort 2, Cohort 3 |
| BevacizumabBevacizumab 10 mg/kg administered intravenously every 2 weeks in 28-day cycles until disease progression, development of unacceptable toxicity or withdrawal of consent. | Drug | Cohort 1 |
Primary outcome
Progression Free Survival (PFS) Rate at Month 6
Time frame: 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.
6 secondary outcomes
Objective Response Rate (ORR)
Time frame: 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)
Progression Free Survival
Time frame: 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)
Overall Survival (OS)
Time frame: 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)
Disease Control Rate (DCR)
Time frame: 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)
Clinical Benefit Rate (CBR)
Time frame: 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)
Number of Participants With Adverse Events (AEs)/Serious Adverse Events (SAEs) as a Measure of Safety
Time frame: 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eisai Medical Services study director
Eisai Inc.
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lenvatinib and Bevacizumab in people with Glioma, run by Eisai Inc. at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) Rate at Month 6 (time frame: At Month 6 from randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2022.