A Study in Subjects With Recurrent Malignant Glioma
Condition: Glioma
MeSH terms: Glioma
Intervention: Lenvatinib; Bevacizumab
Intervention description: 24 mg lenvatinib capsules orally, once daily continuously in 28-day cycles until disease progression, development of unacceptable toxicity or withdrawal of consent.; Bevacizumab 10 mg/kg administered intravenously every 2 weeks in 28-day cycles until disease progression, development of unacceptable toxicity or withdrawal of consent.
Intervention MeSH terms: Bevacizumab; Lenvatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 151.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No

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.