Phase I, Open Label Trial to Explore Safety of Combining BIBW 2992 and Radiotherapy With or Without Temozolomide in Newly Diagnosed GBM

Number of Patients With Investigator Defined Dose Limiting Toxicities (DLT) During the RT Phase

时间窗: 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

时间窗: 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).