BIBF 1120 for Recurrent High-Grade Gliomas

Study Overview
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Brief Summary
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BIBF 1120 is a newly discovered compound that may stop cancer cells from growing abnormally. This drug is currently being used in treatment for other cancers in research studies and information from those other research studies suggests that this agent, BIBF 1120, may help to stop recurrent malignant glioma cells from multiplying and it may also prevent the growth of new blood vessels at the site of the tumor. In this research study, the investigators are looking to see how well BIBF 1120 works in patients with recurrent malignant gliomas.

Detailed Description
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This is a two arm, multicenter, open label phase II trial in adult patients with recurrent supratentorial high-grade glioma. One arm (the bevacizumab naïve arm) will enroll patients who have not received prior bevacizumab therapy, and the other arm (the post-bevacizumab arm) will enroll patients who have experienced progression on bevacizumab. All subjects will receive BIBF 1120 at 200mg orally, twice daily in cycles of 28 days. Subjects will come to the clinic on Day 1 of each cycle (or within 2 days prior) for blood and urine tests and a physical and neurologic exam. Bloods will also be checked within 2 days before or after Day 15 of Cycles 1 and 2. An additional blood sample will be taken on Days 1 and 8 of Cycle 1, at the start of every even-numbered cycle, and at the end of active study treatment. Subjects will have gadolinium-enhanced brain MRI scans performed with tumor measurements at screening, at the start of even-numbered cycles, and at the end of active study treatment(unless already obtained within 4 weeks of completing study treatment). 40 study subjects will have diffusion- and perfusion-weighted MRI at baseline, after 1 week on therapy (± 2 days), within 2 days prior to the start of every even-numbered cycle, and at the end of treatment (unless already obtained within 4 weeks of completing study treatment).

Official Title
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Phase II Trial of Triple Receptor Tyrosine Kinase Receptor Inhibitor BIBF 1120 in Recurrent High-Grade Gliomas

Conditions
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Glioblastoma, Gliosarcoma, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Anaplastic Oligoastrocytoma

Intervention / Treatment
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* Drug: BIBF 1120


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathologically-confirmed, supratentorial, recurrent glioblastoma; subjects with an initial diagnosis of a lower grade glioma are eligible if a subsequent biopsy is determined to be glioblastoma Demonstration of recurrent disease on MRI following prior therapy Development of progressive disease after having received prior RT, and must have an interval of at least 12 weeks from the completion of any radiation therapy to study entry (unless progressive tumor growth is outside the radiation field or there is histopathological confirmation of recurrent tumor). Bi-dimensionally measurable disease (minimum measurement of 1 cm in one dimension) on MRI performed within 14 days prior to first treatment. (If receiving corticosteroids, participants must be on a stable or decreasing dose of corticosteroids for at least 5 days prior to baseline MRI.) Life expectancy of at least 12 weeks KPS >/= 60 Normal organ and marrow function as defined by protocol Recovered from toxic effects of prior therapy Sufficient tumor availability (at least 15-20 unstained paraffin slides from any prior surgery) Exclusion Criteria: Receiving other investigational agent More than 2 prior relapses Prior therapy with inhibitor of VEGF, VEGFR, PDGFR, or FGFR (including bevacizumab) Pregnant or breast-feeding Unwilling to agree to adequate contraception, if subject is of child-bearing potential History of allergic reactions attributed to compounds of similar chemical or biologic composition to BIBF 1120 Use of EIAEDs within 14 days of registration Evidence of recent hemorrhage on baseline MRI of the brain Uncontrolled intercurrent illness Uncontrolled hypertension History of hypertensive encephalopathy History of any of the following within 6 months prior to enrollment: myocardial infarction or unstable angina, stroke or transient ischemic attack, significant vascular disease or peripheral arterial thrombosis, abdominal fistula, gastrointestinal perforation, or intra-abdominal abcess, intracerebral abscess Evidence of bleeding diathesis or coagulopathy Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks prior to the first treatment day, or anticipation of need for major surgical procedure during the course of the study Minor surgical procedures, stereotactic biopsy, fine needle aspiration, or core biopsy within 7 days prior to the first treatment day Serious non-healing wound, ulcer, or bone fracture History of a different malignancy unless disease-free for at least 5 years (unless cervical cancer in situ, or basal cell or squamous cell carcinoma of the skin) HIV positive

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bevacizumab Naive<br>Bevacizumab naive subjects | Drug: BIBF 1120<br>* 200 mg BID oral for 28 day cycle<br>|
| Experimental: Prior Bevacizumab<br>Patients previously treated with bevacizumab | Drug: BIBF 1120<br>* 200 mg BID oral for 28 day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-Month Progression Free Survival | To determine the efficacy of BIBF 1120 in bevacizumab-naive participants with recurrent glioblastoma (GBM) as measured by 6-month progression-free survival (PFS6). | Six months | 
| 3-Month Progression Free Survival | To determine the efficacy of BIBF 1120 in bevacizumab-treated participants with recurrent GBM as measured by 3-month progression free survival (PFS3). | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Experiencing Stable Disease (SD) as Their Best Radiographic Response | Best radiographic response in both populations. There were no participants with partial or complete responses, so the results are being reported in the proportion of participants who experienced stable disease (SD) as their best response (as opposed to progressive disease). | 2 years | 
| Overall Survival | Overall survival in both populations | 2 years | 
| Time-to-tumor Progression | Time-to-tumor progression in both populations. | 2 years | 
| Safety Profile as Summarized With Descriptive Statistics (Using Toxicity Data Gathered on Trial) | Safety profile in both populations - as adverse events are posted separately in detail, these results will demonstrate serious adverse events (defined as grades 3-5) that were judged at least possibly related to Nintedanib (BIBF 1120). | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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brain tumor, recurrent disease