Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioblastoma

Brain Neoplasms

Disease Attributes

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

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroepithelioma

All Drugs and Chemicals

Amino Acids

Dacomitinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end. Patients at first recurrence will be enrolled onto 1 of 2 cohorts that will be recruited and analysed independently. Cohort A will include patients who have EGFRvIII mutations. Cohort B will include patients who have EGFR gene amplification but no EGFRvIII mutations.

Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end.

PF-299804 (Dacomitinib)

Juan Sepúlveda, MD

This multicenter, 2-stage, open-label, phase II trial aims to assess the efficacy and safety of dacomitinib in adult patients with recurrent Glioblastoma (GBM) with EGFR gene amplification and/or EGFRvIII mutation.

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.

Phase II Pilot, Prospective, Open Label, Multicenter CT, to Evaluate the Safety and Efficacy of PF299804, a Pan-HER Irreversible Inhibitor, in Patients With Recurrent Glioblastoma With EGFR Amplification or Presence of EGFRvIII Mutation

Percentage of patients who have progressed / no progress after 6 months of treatment in each of the two cohorts.

Type, incidence, severity, frequency, severity and relationship with IMP of reported adverse events, physical examinations and laboratory tests. Toxicity will be classified and tabulated by NCI-CTCAE v 4.0.

According to RANO criteria. Based on neurological symptoms, doses of dexamethasone and radiological response, assessed by the PI of each center. There will be central review of MRI.

Time from randomization to death by any cause.

Time from first objective response up to disease progression according RANO (in patients with objective responses).

Percentage of patients decreasing doses of corticosteroids during treatment.

By means of minimental test, it will be determined the changes in neurological status of patients.

Pfizer

Grupo Español de Investigación en Neurooncología

Reported in the safety population, all patients that received at least one dose of study treatment (n= 49)

Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end. Patients at first recurrence will be enrolled onto 1 of 2 cohorts that will be recruited and analysed independently. Cohort A will include patients who have EGFRvIII mutations. Cohort B will include patients who have EGFR gene amplification but no EGFRvIII mutations.

PF-299804 (Dacomitinib): Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end.

Age, Continuous

Sex: Female, Male

Spain

Region of Enrollment

O6-Methylguanine-DNA Methyltransferase (MGMT) is a DNA repair enzyme that removes alkyl adducts from the O6 position of guanine.

Methylation of the MGMT promoter has been reported in several tumor types.

MGMT methylation status

Mutations in isocitrate dehydrogenase (IDH) 1 and 2 occur in the vast majority of low grade gliomas and secondary high grade gliomas. These mutations change the function of the enzymes, causing increased methylation in gliomas. Gliomas with mutated IDH1 and IDH2 have improved prognosis compared to gliomas with wild-type IDH

IDH1/2 mutational status

The scale was developed by the Eastern Cooperative Oncology Group (ECOG). It describes a patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability (walking, working, etc.). The scale ranges from 0 (fully independent), 1 (Restricted in physically strenuous activity but ambulatory ), 2 (Ambulatory and capable of all selfcare but unable to carry out any work activities), 3 (Capable of only limited selfcare), 4 (Completely disabled) to 5 (death).

ECOG performance status

Important limitations of our study are the small sample size and the nonrandomized design, which preclude drawing firm conclusions, EGFR amplification, which has been used as a primary laboratory assessment, was tested in the primary tumor, and we have no evidence of the stability of this alteration in the recurrent GBs.

Pau Doñate

Cohort A

Cohort B

Patients were analyzed stratified by cohorts according to their EGFR mutational status: Cohort A included patients with EGFR gene amplification without EGFRvIII mutation. Cohort B included patients with EGFR gene amplification and EGFRvIII mutation.

Progression-free Survival (PFS) at Six Months (PFS6m)

Any grade Adverse event

Grade 3 or higher Adverse envent

Safety population. All patients that were enrolled and received at least 1 dose of study treatment

Safety and Tolerability of Oral Administration of PF-00299804.

The analisis was stratified by cohort according to their EGFR mutational status

Anti-tumor Response

Full data set

2 patients were not evaluable because they withdrawn their consent Data is reported stratified by cohort according to their EGFR mutational status

Spots Global Cancer Trial Database for 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.

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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