Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioma

Glioblastoma

Brain Neoplasms

Gliosarcoma

Astrocytoma

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

Dasatinib

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

You will begin study drug regimen on day 1 of cycle 1 w Dasatinib. If you are undergoing Dasatinib pharmacokinetic blood analysis, Dasatinib will be taken alone until initial PK assessments are collected. Erlotinib will be begin after initial Dasatinib PK assessments are collected \& will continue to be administered w Dasatinib on continuous daily dosing schedule. Initial Dasatinib PK assessments will be collected over 24hrs between days 3-7 of cycle 1 \& at end of cycle 1. If you are not undergoing Dasatinib PK collections you will begin both Dasatinib \& Erlotinib together on day 1 of cycle 1. Both drugs will be given in continuous daily oral manner. Cycle is defined as Dasatinib \& Erlotinib given daily for 28 days for purpose of scheduling evaluations.

Erlotinib and Dasatinib

Annick Desjardins, MD, FRCPC

Primary:

To determine maximum tolerated dose \& dose limiting toxicity of dasatinib when combined w erlotinib among pts w recurrent MG

Secondary:

To further evaluate safety \& tolerability of dasatinib + erlotinib To evaluate pharmacokinetics of dasatinib when administered w erlotinib among recurrent MG pts who are on \& not on CYP-3A enzyme inducing anti-epileptic drugs To evaluate for anti-tumor activity with this regimen in this patient population

Tarceva administered on continuous oral dosing schedule at 150 mg/day for pts not on EIAEDs \& 450 mg/day for pts on EIAEDs. Starting dose level of dasatinib will be 100 mg once day via continuous oral daily dosing. Dasatinib will be increased in successive cohorts of enrolled pts. Pts will remain on treatment until excessive toxicity, progressive disease, withdrawal of consent/death.

Pts have confirmed diagnosis of recurrent/progressive WHO gr IV MG / WHO grade III MG. Phase I 3+3 dose escalation design w 2 independently escalated stratum: stratum A-pts not on CYP3A-enzyme inducing anti-epileptic drugs; stratum B-pts on EIAEDs. Assessment of safety will be based mainly on frequency of adverse events, particularly adverse events leading to discontinuation of treatment \& on number of significant lab abnormalities.

Ph I Dasatinib + Erlotinib in Recurrent MG

Phase I Study of Dasatinib Plus Erlotinib in Recurrent Malignant Glioma

Bristol-Myers Squibb

Genentech, Inc.

Duke University

Oligodendroglioma

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Oligoastrocytoma

Anaplastic Oligoastrocytoma

Anticonvulsants

Bevacizumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Bevacizumab administered intravenously at dose 10 mg/kg every 2 wks. Erlotinib administered orally, continuously once daily in fasting state for each 42-day cycle. Dose of erlotinib is based on prior erlotinib monotherapy trial in RMG. It will be 200 mg/day for pts not on cytochrome P450 3A4 (CYP3A4)-enzyme inducing anti-epileptic drugs \& 500 mg/day for pts on EIAEDs.

It is possible that taking erlotinib w regular medications or supplements may change how erlotinib, subject's regular medications, or subject's regular supplements work. Treatment will continue until either evidence of progressive disease, unacceptable toxicity, non-compliance w study follow-up, or withdrawal of consent.

Bevacizumab and Erlotinib

David A. Reardon, MD

Primary objective:

To estimate 6-month progression free survival probability of pts w recurrent malignant gliomas treated w erlotinib + bevacizumab.

Secondary Objectives:

To evaluate safety \& tolerability of erlotinib + bevacizumab among pts w recurrent malignant gliomas To evaluate radiographic response of pts w recurrent malignant gliomas treated w erlotinib + bevacizumab To evaluate pharmacokinetics of erlotinib when administered to pts w recurrent malignant gliomas; \& to examine relationship of clinical response to Epidermal Growth Factor (EGFR) expression, amplification, \& v-III mutation, phosphatase and tensin homolog (PTEN) expression, vascular endothelial growth factor (VEGF) expression, vascular endothelial growth factor receptor 2 (VEGFR-2) \& phosphorylated protein kinase B (PKB/Akt) in archival tumor samples

Exploratory, Phase II study designed to assess anti-tumor activity of combinatorial regimen consisting of erlotinib + bevacizumab among pts w recurrent malignant glioma. Signal transduction inhibitors, such as erlotinib, as well as anti-angiogenic agents, such as bevacizumab, are expected to exert a cytostatic anti-tumor effect. Primary endpoint of study is probability of progression-free survival at 6 months. An important secondary objective is to further assess the safety of erlotinib + bevacizumab for pts w RMG. Pharmacokinetic studies included in protocol will evaluate impact of enzyme-inducing anti-epileptic drugs (EIAEDs) on metabolism of erlotinib.

If study demonstrates that combo regimen of erlotinib + bevacizumab is associated w encouraging anti-tumor activity among pts w recurrent malignant glioma (RMG), further assessment of regimen in additional ph II \& possibly ph III studies, will be considered.

Phase (Ph) II Bevacizumab + Erlotinib for Patients (Pts) With Recurrent Malignant Glioma (MG)

Phase II Trial of Bevacizumab Plus Erlotinib for Patients With Recurrent Malignant Glioma

The proportion of patients alive and progression free at 6 months

The number of participants with complete or partial response as determined by the following criteria:

* Complete response (CR): Disappearance of all enhancing tumor on contrast enhanced MRI scan. Patient must be off steroids or only on adrenal maintenance doses.
* Partial response (PR): Greater than or equal to a 50% reduction in the size (products of the largest perpendicular diameters) for all enhancing lesions. No new lesions may arise. Steroids must be stable or decreasing dose.

Day 1 and Day 42 of Dosing Erlotinib in Cycle 1: Maximum Concentration (ng/mL) (Cmax) for subjects receiving 500 mg (Enzyme-Inducing Anti-epileptic Drug, EIAED) or 200 mg (non-EIAED) Erlotinib

Day 1 and Day 42 of Dosing Erlotinib in Cycle 1: Area under the Curve (ng/mL.h) (AUC) for subjects receiving 500 mg (Enzyme-Inducing Anti-epileptic Drug, EIAED) or 200 mg (non-EIAED) Erlotinib

Archival tumor samples from grade IV participants were examined by immunohistochemistry for biomarkers.

Archival tumor samples from grade IV participants were examined by immunohistochemistry (IHC) for biomarkers. The IHC expression score is the product of the percentage of cancer cells positive for VEGF multiplied by the overall intensity of staining, ranging from 0 to 3+. This produces a score ranging from 0 to 300.

Archival tumor samples from grade IV participants were examined by immunohistochemistry (IHC) for biomarkers. The IHC score is the product of the percentage of cancer cells positive for VEGFR-2 multiplied by the overall intensity of staining, ranging from 0 to 3+. This produces a score ranging from 0 to 300.

Adverse events were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry into ClinicalTrials.gov

All Patients

Who Grade III

WHO Grade IV

Total

Age Continuous

Sex: Female, Male

Dr. David Reardon

6 Month Progression-free Survival

Complete

Partial

Radiographic Response

Day1 Cmax{ng/ml}200mg n=12

Day1 Cmax{ng/ml}500mg n=10

Day42 Cmax{ng/ml}200mg n=9

Day42 Cmax{ng/ml}500mg n=9

22 WHO Grade IV participants were available for pharmacokinetics studies of erlotinib

Pharmacokinetics of Erlotinib: Cmax

Day1 AUC 0-24{ng/ml.h} 200mg n=12

Day1 AUC 0-24{ng/ml.h} 500mg n=10

Day42 AUC 0-24{ng/ml.h}200mg n=9

Day42 AUC 0-24{ng/ml.h}500mg n=9

Pharmacokinetics of Erlotinib: AUC

Positive Expression

Negative Expression

Tumors from 22 GBM participants were available to undergo immunohistochemical staining to identify potential biomarkers of response or survival benefit. One tumor had an insufficient measurement for analysis

Association of Biomarkers and One-year Survival - Epidermal Growth Factor (EGFR)

Tumors from 22 GBM participants were available to undergo immunohistochemical staining to identify potential biomarkers of response or survival benefit.

Association of Biomarkers and One-year Survival - EGFR vIII

Intact

Loss

Tumors from 22 GBM participants were available to undergo immunohistochemical staining to identify potential biomarkers of response or survival benefit. One tumor had an insufficient measurement for analysis.

Association of Biomarkers and One-year Survival - Phosphatase and Tensin Homologue (PTEN)

Tumors from 22 GBM participants were available to undergo immunohistochemical staining to identify potential biomarkers of response or survival benefit. Four tumors had an insufficient measurement for analysis.

Association of Biomarkers and One-year Survival - Phosphorylated Protein Kinase B (pAKT)

Tumors from 22 GBM participants were available to undergo immunohistochemical staining to identify potential biomarkers of response or survival benefit. Six tumors had an insufficient measurement for analysis.

Association of Biomarkers and One-year Survival - Phosphorylated Mitogen-activated Protein Kinase (pMAPK)

Patients Who Survived At Least 1 Year

Patients Who Survived Less Than 1 Year

Association of Biomarkers and One-year Survival - Vascular Endothelial Growth Factor (VEGF)

Association of Biomarkers and One-year Survival - VEGFR-2

WHO Grade III Malignant Glioma

Bevacizumab administered intravenously at dose 10 mg/kg every 2 wks. Erlotinib administered orally, continuously once daily in fasting state for each 42-day cycle. It will be 200 mg/day for pts not on cytochrome P450 3A4 (CYP3A4)-enzyme inducing anti-epileptic drugs \& 500 mg/day for pts on EIAEDs.

WHO Grade III

WHO Grade IV Malignant Glioma

Bevacizumab administered intravenously at dose 10 mg/kg every 2 wks. Erlotinib administered orally, continuously once daily in fasting state for each 42-day cycle. It will be 200 mg/day for pts not on cytochrome P450 3A4 (CYP3A4)-enzyme inducing anti-epileptic drugs \& 500 mg/day for pts on EIAEDs.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ph I Dasatinib + Erlotinib in Recurrent MG	NCT00609999	Glioblastoma Gliosarcoma	Erlotinib and D...	18 Years -	Duke University
Phase (Ph) II Bevacizumab + Erlotinib for Patients (Pts) With Recurrent Malignant Glioma (MG)	NCT00671970	Glioblastoma Gliosarcoma	Bevacizumab and...	18 Years -	Duke University
Phase (Ph) II Bevacizumab + Erlotinib for Patients (Pts) With Recurrent Malignant Glioma (MG)	NCT00671970	Glioblastoma Gliosarcoma	Bevacizumab and...	18 Years -	Duke University
Phase (Ph) II Bevacizumab + Erlotinib for Patients (Pts) With Recurrent Malignant Glioma (MG)	NCT00671970	Glioblastoma Gliosarcoma	Bevacizumab and...	18 Years -	Duke University

Spots Global Cancer Trial Database for recurrent mg

Every month we try and update this database with for recurrent mg cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.