BIBF 1120 for Recurrent High-Grade Gliomas

Phase 2

Completed

Conditions: Glioblastoma
Anaplastic Oligodendroglioma
Anaplastic Oligoastrocytoma
Gliosarcoma
Anaplastic Astrocytoma

Brief Summary: 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: 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).

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Bevacizumab Naive	BIBF 1120	Bevacizumab naive subjects
Prior Bevacizumab	BIBF 1120	Patients previously treated with bevacizumab

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Overall Survival	2 years	Overall survival in both populations
Proportion of Participants Experiencing Stable Disease (SD) as Their Best Radiographic Response	2 years	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).
Time-to-tumor Progression	2 years	Time-to-tumor progression in both populations.
Safety Profile as Summarized With Descriptive Statistics (Using Toxicity Data Gathered on Trial)	2 years	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).

Locations (4): Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
University of Virginia
🇺🇸
Charlottesville, Virginia, United States