Neoplasms

All Conditions

Rare Diseases

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Temozolomide

Afatinib

Antineoplastic Agents, Alkylating

Alkylating Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

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)

Radiotherapy

Escalating dose cohorts during Radiotherapy(RT) period, fixed dose after RT

BIBW2992

Escalating dose cohorts during Radiotherapy(RT) period , fixed dose after RT

Boehringer Ingelheim

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).

Open Label Trial to Explore Safety of Combining Afatinib (BIBW 2992) and Radiotherapy With or Without Temozolomide in Newly Diagnosed Glioblastoma Multiform

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

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.

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). The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).

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 (Cpre,ss) on days 8, 15 and 29.

Patients were administered Afatinib 20 milligram (mg) film-coated tablet once daily orally plus radiotherapy (RT) i.e. focal radiation at a dose of 2 Gray per fraction on 5 days per week for 6 weeks (RT phase) (total dose of 60 Gray (Gy)) plus Temozolomide (TMZ) 75 milligrams per square meter (mg/m2) capsules continuous daily oral dosing. In the maintenance phase after RT, patients stopped TMZ for 4 weeks and restarted TMZ at 150 mg/m2 in cycle 1 and 200 mg/m2 in cycles 2 to 6 on days 1 to 5 of 28-day treatment cycles. Patients were administered Afatinib 40 milligram (mg) film-coated tablet once daily after RT. Dose reductions of Afatinib were allowed if 40 mg or 30 mg were not tolerated. The treatment duration was until tumour progression or occurrence of undue adverse reactions, whichever occurred first.

Afatinib 20 Milligram, Radiotherapy + Temozolomide - Regimen M

Patients were administered Afatinib 30 mg film-coated tablet once daily orally plus radiotherapy (RT) i.e. focal radiation at a dose of 2 Gray per fraction on 5 days per week for 6 weeks (RT phase) (total dose of 60 Gray) plus Temozolomide 75 milligrams per square meter (mg/m2) capsules continuous daily oral dosing. In the maintenance phase after RT, patients stopped TMZ for 4 weeks and restarted TMZ at 150 mg/m2 in cycle 1 and 200 mg/m2 in cycles 2 to 6 on days 1 to 5 of 28-day treatment cycles. Patients were administered Afatinib 40 milligram (mg) film-coated tablet once daily after RT. Dose reductions of Afatinib were allowed if 40 mg or 30 mg were not tolerated. The treatment duration was until tumour progression or occurrence of undue adverse reactions, whichever occurred first.

Afatinib 30 mg, Radiotherapy + Temozolomide - Regimen M

Patients were administered Afatinib 40 mg film-coated tablet once daily orally plus radiotherapy (RT) i.e. focal radiation at a dose of 2 Gray per fraction on 5 days per week for 6 weeks (RT phase) (total dose of 60 Gray) plus Temozolomide 75 milligrams per square meter (mg/m2) capsules continuous daily oral dosing. In the maintenance phase after RT, patients stopped TMZ for 4 weeks and restarted TMZ at 150 mg/m2 in cycle 1 and 200 mg/m2 in cycles 2 to 6 on days 1 to 5 of 28-day treatment cycles. Patients were administered Afatinib 40 milligram (mg) film-coated tablet once daily after RT. Dose reductions of Afatinib were allowed if 40 mg or 30 mg were not tolerated. The treatment duration was until tumour progression or occurrence of undue adverse reactions, whichever occurred first.

Afatinib 40 mg, Radiotherapy + Temozolomide - Regimen M

Patients were administered Afatinib 20/30/40 mg film-coated tablet once daily orally plus radiotherapy (RT) i.e. focal radiation at a dose of 2 Gray per fraction on 5 days per week for 6 weeks (RT phase) (total dose of 60 Gray) plus Temozolomide 75 milligrams per square meter (mg/m2) capsules continuous daily oral dosing. In the maintenance phase after RT, patients stopped TMZ for 4 weeks and restarted TMZ at 150 mg/m2 in cycle 1 and 200 mg/m2 in cycles 2 to 6 on days 1 to 5 of 28-day treatment cycles. Patients were administered Afatinib 40 milligram (mg) film-coated tablet once daily after RT. Dose reductions of Afatinib were allowed if 40 mg or 30 mg were not tolerated. The treatment duration was until tumour progression or occurrence of undue adverse reactions, whichever occurred first.

Total - Regimen M

Patients were administered Afatinib 20 mg film-coated tablet once daily orally plus radiotherapy (RT) i.e. focal radiation at a dose of 2 Gray per fraction on 5 days per week for 6 weeks (RT phase) (total dose of 60 Gray). Patients were administered Afatinib 40 milligram (mg) film-coated tablet once daily in the maintenance phase after RT. The treatment duration was until tumour progression or occurrence of undue adverse reactions, whichever occurred first. Dose reductions were allowed if 40 mg or 30 mg afatinib were not tolerated.

Afatinib 20 mg, Radiotherapy - Regimen U

Patients were administered Afatinib 40 mg film-coated tablet once daily orally plus radiotherapy (RT) i.e. focal radiation at a dose of 2 Gray per fraction on 5 days per week for 6 weeks (RT phase) (total dose of 60 Gray). Patients were administered Afatinib 40 milligram (mg) film-coated tablet once daily in the maintenance phase after RT. The treatment duration was until tumour progression or occurrence of undue adverse reactions, whichever occurred first. Dose reductions were allowed if 40 mg or 30 mg afatinib were not tolerated.

Afatinib 40 mg, Radiotherapy - Regimen U

Patients were administered Afatinib 20/40 mg film-coated tablet once daily orally plus radiotherapy (RT) i.e. focal radiation at a dose of 2 Gray per fraction on 5 days per week for 6 weeks (RT phase) (total dose of 60 Gray). Patients were administered Afatinib 40 milligram (mg) film-coated tablet once daily in the maintenance phase after RT. The treatment duration was until tumour progression or occurrence of undue adverse reactions, whichever occurred first. Dose reductions were allowed if 40 mg or 30 mg afatinib were not tolerated.

Total - Regimen U

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Treated Set (TS): Patients who received at least 1 dose of trial medication were included in the treated set.

Boehringer Ingelheim, Call Center

Treated Set (TS); 3 patients were not evaluable for the determination of the maximum tolerated dose replaced in regimen M. 7 patients were excluded from the Afatinib 40 mg arm regimen U count as these were part of the expansion phase after the Maximum Tolerated Dose (MTD) had been determined.

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

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0)

Maximum Tolerated Dose (MTD) of Afatinib

Missing

The Objective Tumour Response According to the Macdonald Criteria

Cpre, ss, 8

Cpre, ss, 15

Cpre, ss, 29

Treated Set; only evaluable patients were included in the pharmacokinetic analysis

Spots Global Cancer Trial Database for Open Label Trial to Explore Safety of Combining Afatinib (BIBW 2992) and Radiotherapy With or Without Temozolomide in Newly Diagnosed Glioblastoma Multiform

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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