Phase II study of BIBF 1120 in recurrent Glioblastoma multiforme

Phase 1

• Conditions: Relapsed glioblastoma multiforme; MedDRA version: 12.1Level: LLTClassification code 10018337Term: Glioblastoma multiforme

• Registration Number: EUCTR2010-021407-24-DK
• Lead Sponsor: Rigshospitalet

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-10-25
• Last Update Posted: 2 August 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 64

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, througout the study and 3
?months efter 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion 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 inheritated 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Determine the efficacy of this regime, in terms of objective tumour response rate (complete response and partial response) in these patients;Secondary Objective: 1. Determine the clinical benefit rate (CR+PR+SD). <br>2.Determine the progression- free survival in patients with recurrent glioblastoma multiforme treated with BIBF 1120.<br>3.Describe the adverse event profile of this regimen in these patients.<br> 3. Compare pre-vs-post treatment measurements of biomarkers and vascular system/immune <br> system parameters in patients treated wit this regimen.<br> 4. Correlate tumor and blood biomarkers with clinical response in these patients <br> (VEGF, VEGFR1,VEGFR2,Ca-9,TIMP-1,)<br> Blood (validated assays): PIGF, sVEGFR2, bFGF, UPA, UPAR cleavage<br>;Primary end point(s): Objective response rate