BIBF 1120 in Recurrent Glioblastoma Multiforme
Primary Purpose
Recurrent Glioblastoma
Status
Completed
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
BIBF1120
Sponsored by
About this trial
This is an interventional treatment trial for Recurrent Glioblastoma
Eligibility Criteria
Inclusion criteria
- Written informed consent
Histological verification of primary GBM and failure after radiotherapy and TMZ
- Previously received radiotherapy and TMZ
More than 4 weeks since any of the following prior treatments
- Chemotherapy (6 weeks for nitrosureas or mitomycin C)
- Radiotherapy to nontarget lesions or lesions that are not to be biopsied
- Investigational agents
- More than 6 months since prior major surgery or open biopsy and recovered (only 6 weeks required if operation is for recurrent BGM)
- ● ECOG performance status 0-1
- Age > 18 years
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Fertile females must use anticonception (p- pills, IUD, depot injection of gestagen, subdermal
- implantation, hormonal vaginal ring or transdermal depot plaster, throughout the study and 3
- months after discontinuation of study drugs. Fertile men must use dobbelt barrier method
- (preservative with sperm inhibiting creme) or female partner uses the above mentioned
- contraception.
- Fertile males must use preservatives.
Exclusions criteria
- Prior treatment with BIBF 1120 or any other VEGFR inhibitor, except bevacizumab in Group 2
- Chemo-, hormono-, radio-(except for brain and extremities) or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks prior to treatment with the trial drug.
- Persistence of clinically relevant therapy related toxicity from previous chemo and/or radiotherapy
- Treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial
- Therapeutic anticoagulation( except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid<325mg per day
- Major injuries within the past 10 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period
- History of clinically significant haemorrhagic or thromboembolic event in the past 6 months
- Known inherited predisposition to bleeding or thrombosis
- Significant cardiovascular diseases ( i.e. uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion)
- Proteinuria CTCAE grade 2 or greater
- Hepatic function: total bilirubin outside of normal limits; ALT or AST > 1.5 ULN
Coagulation parameters: International normalised ratio ( INR) > 2, prothrombin time
- (PT) and partial thromboplastin time (PTT) > 50% of deviation of institutional ULN
- Absolute neutrophil count ( ANC) < 1500/ml, platelets < 100000/ml, Haemoglobin < 9.0 g/dl
- Other malignancies within the past 5 years other then basal cell skin cancer or carcinoma in situ of the cervix
- Active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy
- Active or chronic hepatitis C and/or B infection
- Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
- Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study.
- Pregnancy or breast feeding
- Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule
- active alcohol or drug abuse
Sites / Locations
- Rigshospitalet
Outcomes
Primary Outcome Measures
Response rate
MacDonald criteria
Secondary Outcome Measures
Adverse events
CTCAE version 4.0
Full Information
NCT ID
NCT01251484
First Posted
December 1, 2010
Last Updated
October 3, 2012
Sponsor
Ulrik Lassen
Collaborators
Boehringer Ingelheim, University of Copenhagen
1. Study Identification
Unique Protocol Identification Number
NCT01251484
Brief Title
BIBF 1120 in Recurrent Glioblastoma Multiforme
Official Title
Phase II Study of BIBF 1120 in Recurrent Glioblastoma Multiforme
Study Type
Interventional
2. Study Status
Record Verification Date
October 2012
Overall Recruitment Status
Completed
Study Start Date
January 2011 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
August 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Ulrik Lassen
Collaborators
Boehringer Ingelheim, University of Copenhagen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
VEGF inhibition by BEV may induce a change in tumor invasiveness and treatment failure is often associated with remote metastases. BEV may stop the growth of tumor cells by blocking blood flow to the tumor. Cediranib, a pan-VEGF inhibitor has shown promising results in recurrent GBM.
VEGF-blocking with small molecules may overcome the mechanism of resistance, and response to BIBF-1120 in such circumstances may open a new treatment option in GBM. In additional, recurrent glioblastomas have an extremely poor prognosis, so innovative therapies are needed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Glioblastoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
BIBF1120
Intervention Description
Tablet 200 mg twice daily until progression
Primary Outcome Measure Information:
Title
Response rate
Description
MacDonald criteria
Time Frame
Response evaluation every 8 weeks
Secondary Outcome Measure Information:
Title
Adverse events
Description
CTCAE version 4.0
Time Frame
Assessed every 2 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria
Written informed consent
Histological verification of primary GBM and failure after radiotherapy and TMZ
- Previously received radiotherapy and TMZ
More than 4 weeks since any of the following prior treatments
Chemotherapy (6 weeks for nitrosureas or mitomycin C)
Radiotherapy to nontarget lesions or lesions that are not to be biopsied
Investigational agents
More than 6 months since prior major surgery or open biopsy and recovered (only 6 weeks required if operation is for recurrent BGM)
● ECOG performance status 0-1
Age > 18 years
Creatinine normal OR creatinine clearance ≥ 60 mL/min
Fertile females must use anticonception (p- pills, IUD, depot injection of gestagen, subdermal
implantation, hormonal vaginal ring or transdermal depot plaster, throughout the study and 3
months after discontinuation of study drugs. Fertile men must use dobbelt barrier method
(preservative with sperm inhibiting creme) or female partner uses the above mentioned
contraception.
Fertile males must use preservatives.
Exclusions criteria
Prior treatment with BIBF 1120 or any other VEGFR inhibitor, except bevacizumab in Group 2
Chemo-, hormono-, radio-(except for brain and extremities) or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks prior to treatment with the trial drug.
Persistence of clinically relevant therapy related toxicity from previous chemo and/or radiotherapy
Treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial
Therapeutic anticoagulation( except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid<325mg per day
Major injuries within the past 10 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period
History of clinically significant haemorrhagic or thromboembolic event in the past 6 months
Known inherited predisposition to bleeding or thrombosis
Significant cardiovascular diseases ( i.e. uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion)
Proteinuria CTCAE grade 2 or greater
Hepatic function: total bilirubin outside of normal limits; ALT or AST > 1.5 ULN
Coagulation parameters: International normalised ratio ( INR) > 2, prothrombin time
- (PT) and partial thromboplastin time (PTT) > 50% of deviation of institutional ULN
Absolute neutrophil count ( ANC) < 1500/ml, platelets < 100000/ml, Haemoglobin < 9.0 g/dl
Other malignancies within the past 5 years other then basal cell skin cancer or carcinoma in situ of the cervix
Active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy
Active or chronic hepatitis C and/or B infection
Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study.
Pregnancy or breast feeding
Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule
active alcohol or drug abuse
Facility Information:
Facility Name
Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
12. IPD Sharing Statement
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BIBF 1120 in Recurrent Glioblastoma Multiforme
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