Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioblastoma

Glioma

Brain Neoplasms

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Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Anaplastic Astrocytoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Etoposide

Bevacizumab

Etoposide phosphate

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Enzyme Inhibitors

Grade III and IV patients will receive: Bevacizumab administered intravenously at dose 10 mg/kg every two weeks. If patient tolerates 1st bevacizumab dose, subsequent doses may be given by local oncologists under direct supervision of Duke investigators. Etoposide administered orally, once daily for 1st 21 days of each 28-day treatment cycle. Dose of Etoposide will be 50 mg/m2/day.

32 pts w recurrent WHO grade III MG \& 27 pts w recurrent WHO grade IV MG will be enrolled in this study. Estimated rate of accrual is 10 pts per month. The estimated date of study completion is 6-9 months from study initiation. Bevacizumab administered intravenously at dose 10 mg/kg every two weeks. If pt tolerates 1st bevacizumab dose, subsequent doses may be given by local oncologists under direct supervision of Duke investigators. Etoposide administered orally, once daily for 1st 21 days of each 28-day treatment cycle. Dose of Etoposide will be 50 mg/m2/day. The Duke investigators will review all la data \& order treatment. Treatment will continue until either evidence of progressive disease, unacceptable toxicity, non-compliance w study follow-up, or withdrawal of consent.

Bevacizumab and Etoposide

David A. Reardon, MD

Primary Objective to estimate 6-month progression free survival probability of patients with recurrent malignant glioma treated with Etoposide + Bevacizumab.

Secondary Objectives To evaluate safety \& tolerability of Etoposide + Bevacizumab among patients with recurrent malignant glioma (RMG).

To evaluate radiographic response, progression free survival \& overall survival of patients with recurrent malignant glioma treated with Etoposide + Bevacizumab.

Exploratory, single-arm, ph II study designed to assess anti-tumor activity of combinatorial regimen consisting of Etoposide + Bevacizumab among patients with RMG. Primary endpoint of study is probability of progression-free survival at 6 months. Important secondary objective is to further assess safety of Etoposide \& Bevacizumab for patients with recurrent malignant glioma.

If study demonstrates that combinatorial regimen of Etoposide + Bevacizumab is associated with encouraging anti-tumor activity among patients with RMG, further assessment of regimen in additional phase II \& possibly phase III studies, will be considered.

Ph II Bevacizumab + Etoposide for Pts w Recurrent MG

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

Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression. Progression was defined as greater than or equal to a 25% increase in the product of the largest perpendicular diameters of any enhancing lesion or any new enhancing tumor on MRI scans.

The percentage of participants with complete or partial response as determined by the following criteria: complete response was defined as complete disappearance on MR/CT of all enhancing tumor and mass effect, off all corticosteroids (or receiving only adrenal replacement doses), accompanied by a stable or improving neurologic examination; partial response was defined as greater than or equal to 50% reduction in tumor size on MR/CT by bi-dimensional measurement, on a stable or decreasing dose of corticosteroids, accompanied by a stable or improving neurologic examination. A confirmation of response was not required.

Number of participants experiencing a non-hematologic toxicity ≥ grade 3 that was possibly, probably, or definitely related to study treatment.

Time in weeks from the start of study treatment to the date of first progression, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve.

Time in weeks from the start of study treatment to date of death due to any cause. Patients alive as of the last follow-up had OS censored at the last follow-up date. Median OS was estimated using a Kaplan-Meier curve.

Genentech, Inc.

Duke University

The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov

Grade III

Grade IV

Total

Age Continuous

Sex: Female, Male

David Reardon, MD

Bevacizumab administered intravenously at dose 10 mg/kg every two weeks. If patient tolerates 1stbevacizumab dose, subsequent doses may be given by local oncologists under direct supervision of Duke investigators. Etoposide administered orally, once daily for 1st 21 days of each 28-day treatment cycle. Dose of Etoposide will be 50 mg/m2/day

6 Month Progression-Free Survival (PFS)

Objective Response Rate

Safety of Study Treatment Regimen

Median Progression-Free Survival

Median Overall Survival (OS)

Overall Study

Irinotecan

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients treated with bevacizumab + temozolomide

Patients treated with bevacizumab and VP-16 (etoposide)

Patients have progressed/had gr3/\> toxicity related to etoposide, with no had progression/gr 3/\> toxicity related to temozolomide, will only be considered for bevacizumab and temozolomide. Bevacizumab intravenously at dose 10mg/kg every other wk. For patients on bevacizumab and temozolomide, temozolomide administered on continuous dosing schedule at 50mg/m2/day.

Temo + Avastin

Patients have progressed/had gr3/\> toxicity related to temozolomide, but have not progressed/gr3/\> toxicity related to etoposide,considered only for bevacizumab and etoposide. Bevacizumab intravenously at dose 10mg/kg every other wk. Patients on bevacizumab and etoposide, etoposide once daily at 50mg/m2/day first 21 days of each 28-day cycle.

VP-16 + Avastin

Primary objective To estimate 6-month progression free survival probability of pts w recurrent GBM treated w bev + either daily temozolomide/etoposide following progression on bev + irinotecan Secondary Objectives To evaluate safety \& tolerability of bev + either daily temozolomide/etoposide among pts w recurrent GBM who have progressed on bev + irinotecan To evaluate radiographic response, progression free survival \& overall survival of pts w recurrent GBM treated w bev + either daily temozolomide/etoposide following progression on bev + irinotecan

This is exploratory, two-arm, phase II study designed to assess anti-tumor activity of bev + either daily temozolomide/etoposide among GBM pts w progressive disease following bev + irinotecan. About 48 participants w recurrent GBM will take part in this study. Approximately 24 participants will receive bev plus temozolomide \& approximately 24 will receive bev + etoposide. Pts must have confirmed diagnosis of GBM \& radiographic evidence of recurrence following prior therapy bev + irinotecan. 24 pts will be enrolled onto each arm of this single-stage study. If 4 or more of these 24 pts live 6/more months without disease progression, treatment regimen will be considered worthy of further investigation. Otherwise, treatment regimen will be determined not worthy of further investigation within pt population. Type I \& II error rates associated w testing are 0.030 \& 0.115 respectively. Management guidelines dose reduction/interruption for temo, etoposide, \& bev.

Ph II Bev + Either Temozolomide/Etoposide for GBM Pts Who Have Failed Bev + Irinotecan

Phase II Study of Bevacizumab Plus Either Temozolomide or Etoposide for (GBM) Patients Who Have Failed Bevacizumab Plus Irinotecan

Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause.

Percentage of participants with an objective response (complete response or partial response) based on modified Macdonald criteria.

Time in months from the start of study treatment to the date of first progression according to Macdonald criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve.

Time in months from the start of study treatment to date of death due to any cause. Patients alive as of the last follow-up had OS censored at the last follow-up date. Median OS was estimated using a Kaplan-Meier curve.

Incidence of ≥Grade 3 treatment related, non-hematologic toxicity

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

Temozolomide Arm

Etoposide Arm

The Primary Outcome Measure is 6 Month Progression-free Survival.

Radiographic Response

Median Progression-free Survival (PFS)

Grade 3 or Greater, Treatment Related, Non-hematologic Toxicities.

Bevacizumab + Temozolomide: Patients who progressed or had grade 3 or greater toxicity related to prior daily etoposide dosing, but have not had prior progression or grade 3 toxicity related to prior daily temozolomide therapy. Patients who have not had prior progression or grade 3 or greater toxicity with either daily temozolomide or etoposide or who have no prior exposure to either will be randomized to one of the groups. Bevacizumab will be administered intravenously at 10mg/kg every other week. Temozolomide will be administered ona continuous daily dosing schedule at 50 mg/m\^2/day.

Bevacizumab + Etoposide: Patients who progressed or had grade 3 or greater toxicity related to prior daily temozolomide dosing, but have not had prior progression or grade 3 or greater toxicity related to prior daily etoposide therapy. Patients who have not had prior progression or grade 3 or greater toxicity with either daily temozolomide or etoposide or who have no prior exposure to either will be randomized to one of the groups. Bevacizumab will be administered intravenously at 10mg/kg every other week. Etoposide will be administered once daily at 50 mg/m\^2/day for the first 21 days of each 28-day cycle.

Anticonvulsants

Patients will be stratified based on whether they are receiving an enzyme-inducing anti-epileptic drug (EIAED). The dose level of vandetanib will be increased in successive cohorts of subjects. Etoposide will be given daily at a dose of 50 mg/ day for 21 days followed by 7 days with no etoposide.

Vandetanib will be given orally once day. Swallow tablet with 240 ml of non-carbonated water. Initial dose is 100 mg/day for stratum 1 \& 200 mg/day for stratum 2. Etoposide will be taken by mouth in capsule form at a flat dose of 50 mg/day for 1st 21 days of 28-day cycle. You will not take etoposide for following 7 days of the cycle.

Vandetanib and Etoposide

Annick Desjardins, MD

Primary Objective: To determine maximum tolerated dose \& dose limiting toxicity of vandetanib when combined with standard dosing of etoposide among patients with recurrent malignant glioma who are on \& not on enzyme-inducing anti-epileptic drugs (EIAEDs) Secondary Objectives: To assess safety \& tolerability of vandetanib + etoposide in this population; To evaluate pharmacokinetics of vandetanib among malignant glioma patients on \& not on EIAEDs when combined with etoposide.

Exploratory Objective: To evaluate for evidence of anti-tumor activity of study regimen among recurrent malignant glioma patients including radiographic response rate, 6-month progression free survival (PFS) rate \& median PFS.

This is open-label, single center, 2-cohort phase I dose-escalation study of vandetanib administered orally on continuous daily dosing schedule + oral etoposide among adult patients with recurrent or relapsing malignant glioma. Patients will be stratified based on whether they are receiving EIAEDs \& each stratum will independently dose escalate. Dose of vandetanib will be increased in successive cohorts of patients. Etoposide will be given daily at a dose of 50mg/day for 21 days followed by 7 days with no etoposide. Cohorts of 3-6 subjects will accrue at each dose level until maximum tolerated dose (MTD) is defined. Subjects will be adult patients with histologically confirmed malignant glioma who are presenting at time of recurrence/relapse. Up to 48 subjects will be enrolled.

Sample size will be based on modified, classical "3+3" dose escalation design. Primary safety \& efficacy analysis will be conducted on all subject data at time all subjects who are still receiving study drug will have completed at least 4 cycles of treatment. Most common adverse events (AEs) associated with vandetanib are rash, diarrhea, \& asymptomatic QTc prolongation. Protracted oral dosing of etoposide is associated with toxicity that is mild in most patients \& consists mainly of myelosuppression \& diarrhea. Less commonly, protracted etoposide dosing has been associated w more significant hematologic toxicity.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ph II Bevacizumab + Etoposide for Pts w Recurrent MG	NCT00612430	Glioblastoma Gliosarcoma	Bevacizumab and...	18 Years -	Duke University
Ph II Bev + Either Temozolomide/Etoposide for GBM Pts Who Have Failed Bev + Irinotecan	NCT00613028	Glioblastoma Gliosarcoma	Temo + Avastin VP-16 + Avastin	18 Years -	Duke University
Ph II Bev + Either Temozolomide/Etoposide for GBM Pts Who Have Failed Bev + Irinotecan	NCT00613028	Glioblastoma Gliosarcoma	Temo + Avastin VP-16 + Avastin	18 Years -	Duke University
Ph I Dose Escalation Trial of Vandetanib in Combo w Etoposide for Malignant Gliomas	NCT00613223	Gliosarcoma Glioblastoma	Vandetanib and ...	18 Years -	Duke University

Spots Global Cancer Trial Database for etopophos

Every month we try and update this database with for etopophos 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.

Spots Global Cancer Trial Database for etopophos

Every month we try and update this database with for etopophos 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.

Every month we try and update this database with for etopophos 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.