Clinical trial NCT01137604: A Study in Subjects With Recurrent Malignant Glioma
Official title: An Open-Label, Three-Cohort, Phase 2 Study of E7080 (Lenvatinib) in Subjects With Recurrent Malignant Glioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioma
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2010-06-04
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: An open-label phase 2, multicenter study in participants with recurrent malignant glioma.


Eligibility criteria: Inclusion Criteria

1. Histologically confirmed diagnosis of Grade 3 or 4 malignant glioma.
2. 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.
3. Karnofsky score of 70% or greater.
4. 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.
5. Adequate renal function, adequate bone marrow function, adequate blood coagulation function and adequate liver function, as defined in protocol.
6. No evidence of hemorrhage on the baseline magnetic resonance imaging (MRI) scan other than in those subjects who are stable grade 1.

Exclusion criteria:

1. Females who are pregnant or breastfeeding.
2. 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).
3. Active infection requiring intravenous antibiotics.
4. Therapeutic anti-coagulation with warfarin, aspirin, nonsteroidal anti-inflammatory drugs or clopidogrel (low molecular weight heparin is acceptable).
5. Subjects with 24-hour urine protein greater than or equal to 1 gm.
6. Prior surgical resection within 4 weeks, or prior stereotactic biopsy within 2 weeks, of Screening Visit.
7. 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.
8. 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.
9. 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.
10. Prolongation of QTc interval to greater than 480 msec.
11. Active hemoptysis (bright red blood of at least 1/2 teaspoon) within 3 weeks prior to the first dose of study drug.

Primary outcomes:
measure: Progression Free Survival (PFS) Rate at Month 6
timeFrame: At Month 6 from randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3)
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 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)
measure: Progression Free Survival
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: 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)
measure: Disease Control Rate (DCR)
timeFrame: 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)
measure: Clinical Benefit Rate (CBR)
timeFrame: 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)
measure: Number of Participants With Adverse Events (AEs)/Serious Adverse Events (SAEs) as a Measure of Safety
timeFrame: 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)
Other outcomes:
Locations:
city: Tampa
country: United States
state: Florida
city: Boston
country: United States
state: Massachusetts
city: Durham
country: United States
state: North Carolina
city: Calgary
country: Canada
city: Toronto
country: Canada
Study officials:
affiliation: Eisai Inc.
name: Eisai Medical Services
role: STUDY_DIRECTOR
References: