Open Label Trial to Explore Safety of Combining Afatinib (BIBW 2992) and Radiotherapy With or Without Temozolomide in Newly Diagnosed Glioblastoma Multiform
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00977431|
Recruitment Status : Completed
First Posted : September 15, 2009
Results First Posted : February 18, 2019
Last Update Posted : February 18, 2019
This study is a phase I, open label trial to determine the Maximum Tolerated Dose (MTD), safety, pharmacokinetics, and efficacy of BIBW 2992 (an epidermal growth factor receptor(EGFR)inhibitor) to be used in combination with:
- radiotherapy alone (in patients with an unmethylated (functioning) MGMT gene regulator) or
- radiotherapy and Temozolomide (in patients with a methylated (silenced) O6-methylguanine-DNA methyltransferase gene (MGMT) to treat newly diagnosed patients with Grade IV Glioblastoma (primary brain cancer).
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma||Drug: Temozolomide Procedure: Radiotherapy Drug: BIBW2992||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||36 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I, Open Label Trial to Explore Safety of Combining BIBW 2992 and Radiotherapy With or Without Temozolomide in Newly Diagnosed GBM|
|Actual Study Start Date :||September 17, 2009|
|Actual Primary Completion Date :||September 12, 2017|
|Actual Study Completion Date :||September 12, 2017|
Experimental: Regimen U
BIBW2992 + Radiotherapy
Day 1 to day 42
Escalating dose cohorts during Radiotherapy(RT) period , fixed dose after RT
Experimental: Regimen M
BIBW2992 + Temozolomide + Radiotherapy
During RT: 75 mg/m2 daily , 4 weeks after RT: given days 1 to 5 of 28 day cycles (150 mg/m2 in cycle 1, 200 mg/m2 in cycle 2 up to cycle 6)
Escalating dose cohorts during Radiotherapy(RT) period, fixed dose after RT
Day 1 to day 42
- Number of Patients With Investigator Defined Dose Limiting Toxicities (DLT) During the RT Phase [ Time Frame: 6 weeks ]
Adverse event (AE) related to afatinib with any one criteria; Hematological: Common terminology criteria for adverse events (CTCAE) Grade 4 neutropenia (Absolute neutrophil count, including bands <500/cubic millimeter (mm³)) for >7 days, CTCAE Grade 3 or 4 neutropenia of any duration associated with fever >38.3 Celsius, CTCAE Grade 3 thrombocytopenia (platelet count <50000 - 25000/mm³), All other toxicities of CTCAE Grade ≥3 leading interruption of treatment > 14 days.
Non-hematological: CTCAE Grade ≥3 nausea or vomiting despite appropriate use of standard anti-emetics for ≥3 days, CTCAE Grade ≥3 diarrhea despite appropriate use of standard anti-diarrheal therapy for ≥3 days, CTCAE Grade ≥3 rash despite standard medical management and lasting >7 days, CTCAE Grade ≥2 cardiac left ventricular function, CTCAE Grade ≥2 worsening of renal function as measured by serum creatinine, newly developed proteinuria or decrease in glomerular filtration rate, All other toxicities of CTCAE Grade ≥3.
- Maximum Tolerated Dose (MTD) of Afatinib [ Time Frame: 6 weeks ]The MTD was defined as the highest afatinib dose level, at which no more than 1 out of 6 patients experienced drug-related DLT, i.e. the highest afatinib dose with a DLT incidence ≤17%. A separate MTD was determined for afatinib and RT (Regimen U), and for afatinib, TMZ, and RT (Regimen M).
- Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) [ Time Frame: From the first administration of trial medication until 4 weeks after the last administration of trial medication, up to approximately 338 weeks ]Incidence and intensity of adverse events (AE) according to Common Terminology Criteria of Adverse Events (CTCAE v.3.0). The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
- The Objective Tumour Response According to the Macdonald Criteria [ Time Frame: From the first administration of trial medication until 4 weeks after the last administration of trial medication, up to approximately 338 weeks ]Objective response was defined as a best overall response of complete response (CR) or partial response (PR). The best overall response was the best overall response to trial medication according to the Macdonald criteria recorded since the first administration of trial medication and until the earliest of disease progression, death, or start of further anti-cancer treatment. Tumour response was assessed based on local radiological image evaluation by the investigators according to the Macdonald criteria: Complete Response (CR): Disappearance of all enhancing tumour on consecutive Magnetic resonance imaging (MRI) scans at least 28 days apart, off steroids, and neurologically stable or improved. Partial Response (PR): At least 50% reduction in size of enhancing tumour on consecutive MRI scans at least 28 days apart, steroids stable or reduced, and neurologically stable or improved.
- Concentration of Afatinib in Plasma at Steady State Pre-dose on Days 8, 15 and 29 [ Time Frame: Pharmacokinetic blood sample were taken at 5 minutes before drug on days 8, 15 and 29 and 1, 3 and 6 hours after drug administration on day 15 ]Concentration of afatinib in plasma at steady state pre-dose (Cpre,ss) on days 8, 15 and 29.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00977431
|Cambridge, United Kingdom, CB2 0QQ|
|Ninewells Hospital & Medical School|
|Dundee, United Kingdom, DD1 9SY|
|Beatson West of Scotland Cancer Centre|
|Glasgow, United Kingdom, G12 0YN|
|The Christie Hospital|
|Manchester, United Kingdom, M20 4BX|
|The Royal Marsden Hospital|
|Sutton, United Kingdom, SM2 5PT|
|Study Chair:||Boehringer Ingelheim||Boehringer Ingelheim|