Ph II Bevacizumab + Etoposide for Pts w Recurrent MG

Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00612430
• Other study ID #: Pro00000379
• Status: Completed
• Phase: Phase 2
• First received: January 29, 2008
• Last updated: July 30, 2013
• Start date: March 2007
• Est. completion date: September 2011

Study information

• Verified date: May 2013
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: September 2011
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioblastoma
• Gliosarcoma

Intervention

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.

Locations

Country	Name	City	State
United States	Duke University Health System	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Objective Response Rate	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 years	No
Secondary	Safety of Study Treatment Regimen	Number of participants experiencing a non-hematologic toxicity = grade 3 that was possibly, probably, or definitely related to study treatment.	2 years	Yes
Secondary	Median Progression-Free Survival	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.	Patients were followed for a median of 91.4 weeks	No
Secondary	Median Overall Survival (OS)	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.	median of 91.4 weeks	No

External Links

•   The Preston Robert Tisch Brain Tumor Center at DUKE