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

NCT00613028 | Completed Phase 2 Results DMC

• 1 other identifier: Pro00003768
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Glioblastoma; Gliosarcoma

Keywords

Glioblastoma; Gliosarcoma; GBM; Bevacizumab; Avastin; Etoposide; Brain tumor; Irinotecan; Glioblastoma multiforme; Temodar; Temozolomide; Etopophos; Toposar; VePesid; VP-16; Camptosar

Outcome Measures

Primary Outcomes (1)

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

  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.

  6 months

Secondary Outcomes (4)

• Radiographic Response

  41 months

• Median Progression-free Survival (PFS)

  41 months

• Median Overall Survival (OS)

  41 months

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

  41 months

Study Arms (2)

Temo + Avastin

EXPERIMENTAL

Patients treated with bevacizumab + temozolomide

Drug: Temo + Avastin

VP-16 + Avastin

EXPERIMENTAL

Patients treated with bevacizumab and VP-16 (etoposide)

Drug: VP-16 + Avastin

Interventions

Temo + Avastin DRUG

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.

Also known as: temozolomide, temodar, bevacizumab

Temo + Avastin

VP-16 + Avastin DRUG

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.

Also known as: VP-16, etoposide, bevacizumab, avastin

VP-16 + Avastin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pts have confirmed diagnosis of GBM \& radiographic evidence of recurrence following prior therapy w bev + irinotecan
• Age \>18 yrs
• Interval of \>4 wks between prior surgical resection/1 week from stereotactic biopsy
• Interval of \>12 wks from end of prior external beam radiation therapy (XRT) unless there is new area of enhancement consistent w recurrent tumor outside of XRT field,/there are progressive changes on MRI on \>2 consecutive MRI scans \>4wks apart, /there is biopsy-proven tumor progression
• Interval of \>4 wks from prior chemo / investigational agent unless pt has recovered from all anticipated toxicities associated w that therapy.
• Eastern Cooperative Oncology Group (ECOG) 0-1
• Hematocrit \>29percent, absolute neutrophil count (ANC)\>1,000 cells/ml l, platelets \> 100,000 cells/ml l
• Serum creatinine\<1.5 mg/dl, serum glutamate oxaloacetate transaminase (SGOT) \& bilirubin\<1.5 times upper limit of normal (ULN)
• Signed informed consent approved by Institutional Review Board (IRB) prior to pt entry
• No evidence of hemorrhage on baseline MRI/CT scan other than those that are stable gr1
• If sexually active, pts will take contraceptive measures for duration of treatments

You may not qualify if:

• Co-medication that may interfere w study results
• Active infection requiring intravenous antibiotics
• Progression to daily etoposide/progression to daily temo
• Gr3/greater toxicity related to prior bev therapy,/prior temozolomide/etoposide
• Requires therapeutic anti-coagulation with warfarin.
• Inability to comply w study and/or follow-up procedures
• Current, recent,/planned participation in experimental drug study other than Genentech-sponsored bev cancer study
• Inadequately controlled hypertension
• Any prior history of hypertensive crisis/hypertensive encephalopathy
• New York Heart Association (NYHA) Gr II/greater congestive heart failure
• History of myocardial infarction (MI)/unstable angina within 6 mths prior to study enrollment
• History of stroke/transient ischemic attack within 6 mths prior to study enrollment
• Significant vascular disease
• Symptomatic peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy

Sponsors & Collaborators

• Duke University: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center at DUKE

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Brain Neoplasms

Interventions

Bevacizumab; Temozolomide; Etoposide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: David A. Reardon, MD
• Organization: Preston Robert Tisch Brain Tumor Center at Duke

reard003@mc.duke.edu

919-668-1409

Study Officials

• David A. Reardon, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2008
• First Posted: February 12, 2008
• Study Start: April 1, 2008
• Primary Completion: October 1, 2009
• Study Completion: January 1, 2011
• Last Updated: July 16, 2013
• Results First Posted: February 4, 2013

Record last verified: 2013-07

Locations

US (1)