Ph II Bevacizumab + Etoposide for Pts w Recurrent MG

• ClinicalTrials.gov Identifier: NCT00612430
• Recruitment Status: Completed
• First Posted: February 11, 2008
• Results First Posted: July 26, 2013
• Last Update Posted: August 12, 2013
• Sponsor: Duke University
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): Duke University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Glioblastoma; Gliosarcoma	Drug: Bevacizumab and Etoposide	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 59 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Bevacizumab Plus Etoposide for Patients With Recurrent Malignant Glioma
• Study Start Date: March 2007
• Actual Primary Completion Date: September 2008
• Actual Study Completion Date: September 2011

Arms and Interventions

Arm

Intervention/treatment

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

Outcome Measures

Primary Outcome Measures :

1. 6 Month Progression-Free Survival (PFS) [ Time Frame: 6 months ]
   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 :

1. Objective Response Rate [ Time Frame: 2 years ]
   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.
2. Safety of Study Treatment Regimen [ Time Frame: 2 years ]
   Number of participants experiencing a non-hematologic toxicity ≥ grade 3 that was possibly, probably, or definitely related to study treatment.
3. Median Progression-Free Survival [ Time Frame: Patients were followed for a median of 91.4 weeks ]
   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.
4. Median Overall Survival (OS) [ Time Frame: median of 91.4 weeks ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, North Carolina

Duke University Health System

Durham, North Carolina, United States, 27710

Sponsors and Collaborators

Duke University

Genentech, Inc.

Investigators

• Principal Investigator: David A. Reardon, MD; Duke Health

More Information

Additional Information:

The Preston Robert Tisch Brain Tumor Center at DUKE 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT00612430
• Other Study ID Numbers: Pro00000379
• First Posted: February 11, 2008
• Results First Posted: July 26, 2013
• Last Update Posted: August 12, 2013
• Last Verified: May 2013

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; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Bevacizumab; Etoposide; Etoposide phosphate; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action