Safety and Efficacy of PF-299804 (Dacomitinib), a Pan-HER Irreversible Inhibitor, in Patients With Recurrent Glioblastoma With EGFR Amplification or Presence of EGFRvIII Mutation. A Phase II CT.

Exclusion Criteria

• •4. Patients in first relapse (or progression) to chemo-radiotherapy and temozolomide-based chemotherapy (Stupp4 scheme).
• •5. All patients must have EGFR gene amplification by in situ hybridization fluorescent (FISH) and / or EGFRvIII mutation by PCR in tumor samples made by the central laboratory (Laboratory of Neuropathology. Hospital Universitario 12 de Octubre).
• •6. For all study cohorts, patients must be at least 15 unstained slides or a block of paraffin-embedded tissue available from a previous biopsy or surgery (archived tumor samples previously).
• •7. All patients must show progressive disease of the brain MRI is as defined in the Criteria RANO.
• •8. Interval of at least one week between prior intra-cranial biopsy, healed properly, and inclusion.
• •9. Interval of at least 12 weeks between prior radiotherapy and inclusion, unless: a) histopathologic confirmation of recurrent tumor, or b) MR recurrence outside the radiation field.
• •10. Patients must have recovered from previous therapy: 28 days from the completionof any investigational drug and / or the termination of any cytotoxic therapy.
• •11. ECOG performance status less than or equal to 2.
• •12. Stable or decreasing doses of corticosteroids during the five days prior to inclusion in the study.
• •13. Adequate bone marrow reserve, hematocrit greater than or equal to 29%, WBC\> 3000 / mcl,ANC greater than or equal to 1,500 cells / ul, platelets greater than or equal a100.000 cells / ul.
• •14. Adequate hepatic function: bilirubin less than or equal to 1.5 times ULN, AST (SGOT) less than or equal to 2.5 x ULN.
• •15. Creatinine within the center ULN or creatinine clearance \> 60 mL/min/1.73 m2 for subjects with creatinine levels above the center ULN.
• •16. The patients in whom resection was made in the first tumor recurrence are eligible in the following cases:
• •* There is adequate recovery from surgery.
• •* There must be measurable or evaluable disease after surgery. For an adequate Radiological evaluation of residual disease, MRI must be completed within 72 hours after surgery or 4 weeks after surgery.
• •17. The effects of PF-00299804 in human foetal development are unknown. For this reason, women of childbearing potential and men must agree to use effective contraception (hormonal control method, barrier, abstinence or surgical sterilization) before inclusion in the study, during participating in the study and at least 3 months after treatment has ended the trial. The definition of an effective contraceptive method is based on the criterion of the principal investigator or designee. In case of a woman become pregnant or there is suspicion that she is pregnant while participating in this study, the trial physician must inform immediately. All women of childbearing potential must have a negative pregnancy test (serum / urine) in the 2 weeks before the start of treatment. NOTE: Patients who have received treatment based on the scheme Stupp (Chemoradiotherapy with temozolomide followed by temozolomide sequential) are eligible in the trial, even if other drugs have been added to this scheme. It is excluded from this, those patients who have been treated with EGFR inhibitors for obvious reasons. However, those patients who have received Stupp scheme + other drugs like bevacizumab and cilengitide, remain eligible.
• •1. Presence of extra-cranial metastatic disease.
• •2. Concomitant treatment with other investigational drugs.
• •3. Prior treatment with an investigational drug/s known or are suspected to be active by the action of any component of the EGFR tyrosine kinase.
• •4. Surgery of any kind (does not include diagnostic procedures such as minor lymph node biopsy) in the 2 weeks prior to baseline assessments of the disease, or presence of side effects of previous procedures.
• •5. Presence of any clinically significant gastrointestinal abnormality that can affect oral administration, transit or absorption of study drug, such as the inability to take medication by mouth as tablets.
• •6. Presence of any psychiatric or cognitive disorder that limits the understanding or the signature of informed consent and / or jeopardize the fulfillment of the requirements of this protocol.
• •7. Significant or uncontrolled cardiovascular disease, including:
• •* Myocardial infarction within the previous 12 months
• •* Uncontrolled angina within the previos 6 months
• •* Congestive heart failure in the previous 6 months
• •* Known or suspected congenital long QT syndrome
• •* History of clinically significant ventricular arrhythmias of any type (as ventricular tachycardia, ventricular fibrillation or torsades de pointes)
• •* QTc prolongation on electrocardiogram prior to entry (\> 470 msec)