Ph II Bevacizumab + Etoposide for Pts w Recurrent MG

This study has been completed.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00612430
First received: January 29, 2008
Last updated: July 30, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Glioblastoma
Gliosarcoma
Drug: Bevacizumab and Etoposide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Bevacizumab Plus Etoposide for Patients With Recurrent Malignant Glioma

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • 6 Month Progression-Free Survival (PFS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Objective Response Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.

  • Safety of Study Treatment Regimen [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Number of participants experiencing a non-hematologic toxicity ≥ grade 3 that was possibly, probably, or definitely related to study treatment.

  • Median Progression-Free Survival [ Time Frame: Patients were followed for a median of 91.4 weeks ] [ Designated as safety issue: No ]
    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.

  • Median Overall Survival (OS) [ Time Frame: median of 91.4 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 59
Study Start Date: March 2007
Study Completion Date: September 2011
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab + Etoposide
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
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.
Other Names:
  • Bevacizumab - Avastin
  • Etoposide-Etopophos-Toposar-VePesid-VP-16

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00612430

Locations
United States, North Carolina
Duke University Health System
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Genentech
Investigators
Principal Investigator: David A. Reardon, MD Duke University Health System
  More Information

Additional Information:
No publications provided by Duke University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00612430     History of Changes
Other Study ID Numbers: Pro00000379
Study First Received: January 29, 2008
Results First Received: May 28, 2013
Last Updated: July 30, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
Glioblastoma
Gliosarcoma
GBM
MG
Brain tumor
Bevacizumab
Avastin
Etoposide
VP-16
Etopophos
Toposar
VePesid
Glioblastoma multiforme
Recurrent GBM
Anaplastic astrocytoma
Malignant glioma

Additional relevant MeSH terms:
Glioblastoma
Gliosarcoma
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Etoposide
Etoposide phosphate
Bevacizumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014