Ph II Bevacizumab + Etoposide for Pts w Recurrent MG

NCT00612430 | Completed Phase 2 Results DMC

• 1 other identifier: Pro00000379
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Glioblastoma; Gliosarcoma

Keywords

Glioblastoma; Gliosarcoma; GBM; MG; Brain tumor; Bevacizumab; Avastin; Etoposide; VP-16; Etopophos; Toposar; VePesid; Glioblastoma multiforme; Recurrent GBM; Anaplastic astrocytoma; Malignant glioma

Outcome Measures

Primary Outcomes (1)

• 6 Month Progression-Free Survival (PFS)

  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.

  6 months

Secondary Outcomes (4)

• Objective Response Rate

  2 years

• Safety of Study Treatment Regimen

  2 years

• Median Progression-Free Survival

  Patients were followed for a median of 91.4 weeks

• Median Overall Survival (OS)

  median of 91.4 weeks

Study Arms (1)

Bevacizumab + Etoposide

EXPERIMENTAL

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.

Drug: Bevacizumab and Etoposide

Interventions

Bevacizumab and Etoposide DRUG

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.

Also known as: Bevacizumab - Avastin, Etoposide-Etopophos-Toposar-VePesid-VP-16

Bevacizumab + Etoposide

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 recurrent/progressive WHO gr III \& IV MG
• Age \>18 rs
• Interval of \>4 wks since prior surgery
• Interval of \>4 wks since prior XRT/chemo, unless there is unequivocal evidence of progressive disease \& pts have recovered from all anticipated toxicity of most recent therapy;
• Karnofsky performance status score \>60
• Hematocrit \>29 percent, ANC \>1,500 cells/microliter, platelets \>100,000 cells/microliter
• Serum creatinine \<1.5 mg/dl, BUN \<25 mg/dl, serum SGOT \& bilirubin \<1.5 x ULN
• For pts on corticosteroids, they have been on astable dose for 1wk prior to entry
• Signed informed consent approved by IRB prior to pt entry
• If sexually active, pts must agree to take contraceptive measures for duration of treatments.

You may not qualify if:

• Prior therapy w either bevacizumab/etoposide
• \>3 prior recurrences
• Pregnancy/breast feeding
• Co-medication w immuno-suppressive agents other than corticosteroids including but not limited to cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil
• Evidence of CNS hemorrhage on baseline MRI on CT scan
• Pts who require therapeutic anti-coagulation
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics \& psychiatric illness/social situations that would limit compliance w study requirements, or disorders associated w significant immunocompromised state
• Pts w another primary malignancy that has required treatment \<past year

Sponsors & Collaborators

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

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Reardon DA, Desjardins A, Vredenburgh JJ, Gururangan S, Sampson JH, Sathornsumetee S, McLendon RE, Herndon JE 2nd, Marcello JE, Norfleet J, Friedman AH, Bigner DD, Friedman HS. Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study. Br J Cancer. 2009 Dec 15;101(12):1986-94. doi: 10.1038/sj.bjc.6605412. Epub 2009 Nov 17.

  PMID: 19920819 DERIVED

Related Links

• The Preston Robert Tisch Brain Tumor Center at DUKE

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Brain Neoplasms; Astrocytoma; Glioma

Interventions

Bevacizumab; Etoposide

Condition Hierarchy (Ancestors)

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; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: David Reardon, MD
• Organization: Duke University Medical Center

David_Reardon@DFCI.harvard.edu

919-668-2329

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2008
• First Posted: February 11, 2008
• Study Start: March 1, 2007
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2011
• Last Updated: August 12, 2013
• Results First Posted: July 26, 2013

Record last verified: 2013-05

Locations

US (1)