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Treatment Name: |
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BIBW 2992 with or without daily temozolomide in the treatment of
patients with recurrent malignant glioma
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Phase: |
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Phase 1/2 |
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Treatment ID#: |
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1889 |
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Age Group: |
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Adults Only |
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Min Karnofsky Score: |
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60: Requires occasional assistance but is able to care for most of own needs |
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Conditions: |
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Prior Surgery is Allowed
Prior Radiation is Allowed
Prior Chemotherapy is Allowed
Exclusions:
1.Less than 12 weeks between radiotherapy and start of study treatment, unless new
enhancing lesion outside of radiation field or radiologically progressive on two
consecutive MRI scans at least four weeks apart or biopsy-proven recurrence.
2. Less than two weeks from surgical resection (one week from prior stereotactic biopsy)
or major surgical procedure.
3. Less than two weeks after previous chemotherapy (6 weeks from nitrosureas).
4. Less than four weeks from prior treatment with bevacizumab.
5. Treatment with other investigational drugs; participation in another clinical study
within the past 2 weeks before start of therapy or concomitantly with this study.
6. Progressive disease or toxicity =CTCAEv3 Grade 3 to protracted temozolomide
dosing (defined as temozolomide administered more than 5 days/28 day cycle).
7. Active infectious disease requiring intravenous therapy.
8. Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
9. Gastrointestinal disorders that may interfere with the absorption of the study drug or
chronic diarrhea.
10. Serious illness or concomitant non-oncological disease considered by the investigator
to be incompatible with the protocol.
11. Patient is <3 years free of another primary malignancy except: if the other primary
malignancy is either not currently clinically significant or does not require active
intervention (such as a basal cell skin cancer or a cervical carcinoma in situ).
Existence of any other malignant disease is not allowed.
12. Cardiac left ventricular function with resting ejection fraction <50%.
13. Absolute neutrophil count (ANC) less than 1500/mm3.
14. Platelet count less than 100,000/mm3.
15. Bilirubin greater than 1.5 x upper limit of institutional norm.
16. Aspartate amino transferase (AST) greater than 3 x upper limit of institutional norm.
17. Serum creatinine greater than 1.5 x upper limit of institutional norm.
18. Patients who are sexually active and unwilling to use a medically acceptable method
of contraception.
19. Pregnancy or breast-feeding.
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Last Updated: |
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10/20/2008 |
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Tumor Types: |
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Anaplastic Astrocytoma
Glioblastoma Multiforme
Oligodendroglioma High Grade |
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Comments: |
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BIBW 2992 is a highly potent and irreversible inhibitor of the EGFR and HER2 tyrosine
kinases.
BIBW 2992 inhibits EGFR/HER2 tyrosine kinases both in vitro and in vivo. The in vitro
potency of BIBW 2992 has been determined in enzymatic assays using the human EGFR and
HER2 protein kinase domains as well as in cellular assays measuring the inhibition of either
receptor phosphorylation or proliferation. The potency of BIBW 2992 on the EGFR and
HER2 kinases revealed IC50 values of 0.5 nM and 14 nM, respectively. BIBW 2992 is highly
selective for these kinases and no additional inhibition of other kinases has been observed.
The inhibitory activity of BIBW 2992 on EGFR and HER2 was confirmed at the cellular
level. This compound prevents EGF-stimulated transphosphorylation and induces the
dephosphorylation of constitutively activated HER2, in different cell lines, in the nanomolar
range.
In summary, BIBW 2992 is effective in mechanism and disease-related in vitro and in vivo
models. Tumor regression was achieved in all models upon treatment with BIBW 2992. The
necessary maximum plasma concentration in nude mice to reach this effect was 300 nM.
Thus, BIBW 2992 is a potent, irreversible, orally available EGFR/HER2 tyrosine kinase
inhibitor displaying significant anti-tumor activity in a once daily dosing schedule.
BIBW 2992 did not show relevant inhibition of cytochrome P450 isoenzymes. However,
BIBW 2992 is a CYP3A4 substrate (U05-1723-01), although this metabolic pathway is not
the dominant one. Therefore, drug-drug interactions with CYP3A4 inducers or inhibitors are
not expected.
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Treatment Type: |
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Less-Toxics |
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Contact: |
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David Schiff MD
Co-Director, Division of Neuro-Oncology
University of Virginia Health System
Department of Neurology
Box 800432
Charlottesville, VA 22908-0432 USA
Phone: 434-982-4415
Fax: 434-982-4467
E-mail: ds4jd@virginia.EDU
Website: www.uvabraintumor.com |
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- Last updated refers to the date when our listing for each treatment was last updated.
- ID is a combination of our internal ID and the official ID for the trial, if any.
- Min Karnofsky is a general guide to how well you have to function to use this treatment
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