Relapsed glioblastoma multiforme MedDRA version: 12.1 Level: LLT Classification code 10018337 Term: Glioblastoma multiforme
Conditions
Interventions
Product Name: BIBF1120
Product Code: BIBF1120
Pharmaceutical Form: Capsule*
Sponsors
Rigshospitalet
Eligibility
Sex/Gender
All
Inclusion 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, 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
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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). 2. Determine the progression- free survival in patients with recurrent glioblastoma multiforme treated with BIBF 1120. 3. Describe the adverse event profile of this regimen in these patients. 3. Compare pre-vs-post treatment measurements of biomarkers and vascular system/immune system parameters in patients treated wit this regimen. 4. Correlate tumor and blood biomarkers with clinical response in these patients (VEGF, VEGFR1,VEGFR2,Ca-9,TIMP-1,) Blood (validated assays): PIGF, sVEGFR2, bFGF, UPA, UPAR cleavage ;Primary end point(s): Objective response rate | — |
Countries
Denmark
Outcome results
None listed