BIBF 1120 for Recurrent High-Grade Gliomas
Primary Purpose
Glioblastoma, Gliosarcoma, Anaplastic Astrocytoma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
BIBF 1120
Sponsored by
About this trial
This is an interventional treatment trial for Glioblastoma focused on measuring brain tumor, recurrent disease
Eligibility Criteria
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
Sites / Locations
- Massachusetts General Hospital
- Dana-Farber Cancer Institute
- Cleveland Clinic
- University of Virginia
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Bevacizumab Naive
Prior Bevacizumab
Arm Description
Bevacizumab naive subjects
Patients previously treated with bevacizumab
Outcomes
Primary Outcome Measures
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).
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).
Secondary Outcome Measures
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).
Overall Survival
Overall survival in both populations
Time-to-tumor Progression
Time-to-tumor progression in both populations.
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).
Full Information
NCT ID
NCT01380782
First Posted
June 21, 2011
Last Updated
August 15, 2014
Sponsor
Patrick Y. Wen, MD
Collaborators
Boehringer Ingelheim, Wake Forest University Health Sciences, University of Virginia, Massachusetts General Hospital, The Cleveland Clinic
1. Study Identification
Unique Protocol Identification Number
NCT01380782
Brief Title
BIBF 1120 for Recurrent High-Grade Gliomas
Official Title
Phase II Trial of Triple Receptor Tyrosine Kinase Receptor Inhibitor BIBF 1120 in Recurrent High-Grade Gliomas
Study Type
Interventional
2. Study Status
Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
July 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Patrick Y. Wen, MD
Collaborators
Boehringer Ingelheim, Wake Forest University Health Sciences, University of Virginia, Massachusetts General Hospital, The Cleveland Clinic
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma, Gliosarcoma, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Anaplastic Oligoastrocytoma
Keywords
brain tumor, recurrent disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bevacizumab Naive
Arm Type
Experimental
Arm Description
Bevacizumab naive subjects
Arm Title
Prior Bevacizumab
Arm Type
Experimental
Arm Description
Patients previously treated with bevacizumab
Intervention Type
Drug
Intervention Name(s)
BIBF 1120
Intervention Description
200 mg BID oral for 28 day cycle
Primary Outcome Measure Information:
Title
6-Month Progression Free Survival
Description
To determine the efficacy of BIBF 1120 in bevacizumab-naive participants with recurrent glioblastoma (GBM) as measured by 6-month progression-free survival (PFS6).
Time Frame
Six months
Title
3-Month Progression Free Survival
Description
To determine the efficacy of BIBF 1120 in bevacizumab-treated participants with recurrent GBM as measured by 3-month progression free survival (PFS3).
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Proportion of Participants Experiencing Stable Disease (SD) as Their Best Radiographic Response
Description
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 Frame
2 years
Title
Overall Survival
Description
Overall survival in both populations
Time Frame
2 years
Title
Time-to-tumor Progression
Description
Time-to-tumor progression in both populations.
Time Frame
2 years
Title
Safety Profile as Summarized With Descriptive Statistics (Using Toxicity Data Gathered on Trial)
Description
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).
Time Frame
2 years
Other Pre-specified Outcome Measures:
Title
Exploratory Objective #1: Progression-free Survival at 3- and 6-months for Participants With Recurrent Anaplastic Gliomas (AG)
Description
To explore the efficacy of BIBF 1120 in bevacizumab-naïve and bevacizumab-treated participants with recurrent anaplastic gliomas (AG) survival was assessed at 6 months for Arm A and 3 months for Arm B.
Time Frame
Arm A - 6 months; Arm B - 3 months
Title
Exploratory Objective #2: Determination if Any Correlation Exists Between Patient Outcomes (Survival, PFS3, PFS6) and Tumor Genotype and/or Expression Profile
Description
To explore the extent to which the tumor's genotype and expression profile correlate with outcome.
Time Frame
2 years
Title
Exploratory Objective #3: Determination if Any Correlation Exists Between Patient Outcomes (Survival, PFS3, PFS6) and Serum Angiogenic Peptides, Circulating Endothelial Cells, and/or Circulating Progenitor Cells
Description
To explore the correlation between serum angiogenic peptides, circulating endothelial cells, and circulating progenitor cells with response to therapy.
Time Frame
2 years
Title
Exploratory Objective #4: Determination if Any Correlation Exists Between Patient Outcomes (Survival, PFS3, PFS6) and Perfusion MRI, Diffusion MRI
Description
To explore the correlation between perfusion MRI, diffusion MRI and response to therapy.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Y Wen, M.D.
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908-4324
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
25338318
Citation
Norden AD, Schiff D, Ahluwalia MS, Lesser GJ, Nayak L, Lee EQ, Rinne ML, Muzikansky A, Dietrich J, Purow B, Doherty LM, LaFrankie DC, Pulverenti JR, Rifenburg JA, Ruland SF, Smith KH, Gaffey SC, McCluskey C, Ligon KL, Reardon DA, Wen PY. Phase II trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas. J Neurooncol. 2015 Jan;121(2):297-302. doi: 10.1007/s11060-014-1631-y. Epub 2014 Oct 22.
Results Reference
derived
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BIBF 1120 for Recurrent High-Grade Gliomas
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