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

July 10, 2013 updated by: Duke University

Phase II Study of Bevacizumab Plus Either Temozolomide or Etoposide for (GBM) Patients Who Have Failed Bevacizumab Plus Irinotecan

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is exploratory, two-arm, phase II study designed to assess anti-tumor activity of bev + either daily temozolomide/etoposide among GBM pts w progressive disease following bev + irinotecan. About 48 participants w recurrent GBM will take part in this study. Approximately 24 participants will receive bev plus temozolomide & approximately 24 will receive bev + etoposide. Pts must have confirmed diagnosis of GBM & radiographic evidence of recurrence following prior therapy bev + irinotecan. 24 pts will be enrolled onto each arm of this single-stage study. If 4 or more of these 24 pts live 6/more months without disease progression, treatment regimen will be considered worthy of further investigation. Otherwise, treatment regimen will be determined not worthy of further investigation within pt population. Type I & II error rates associated w testing are 0.030 & 0.115 respectively. Management guidelines dose reduction/interruption for temo, etoposide, & bev.

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Health System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
  • Serious, non-healing wound, ulcer, or bone fracture
  • Proteinuria at screening as demonstrated by either:
  • urine protein:creatinine (UPC) ratio >1.0 at screening /
  • Urine dipstick for proteinuria ≥ 2+
  • Known hypersensitivity to any component of bevacizumab
  • Pregnant or lactating. Use of effective means of contraception in subjects of child-bearing potential

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Temo + Avastin
Patients treated with bevacizumab + temozolomide
Drug: Temo + Avastin
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.
Other Names:
  • bevacizumab
  • temodar
  • temozolomide
EXPERIMENTAL: VP-16 + Avastin
Patients treated with bevacizumab and VP-16 (etoposide)
Drug: VP-16 + Avastin
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.
Other Names:
  • VP-16
  • bevacizumab
  • etoposide
  • avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Primary Outcome Measure is 6 Month Progression-free Survival.
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 according to the Macdonald criteria, or to death due to any cause.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Radiographic Response
Time Frame: 41 months
Percentage of participants with an objective response (complete response or partial response) based on modified Macdonald criteria.
41 months
Median Progression-free Survival (PFS)
Time Frame: 41 months
Time in months from the start of study treatment to the date of first progression according to Macdonald criteria, 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.
41 months
Median Overall Survival (OS)
Time Frame: 41 months
Time in months 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.
41 months
Grade 3 or Greater, Treatment Related, Non-hematologic Toxicities.
Time Frame: 41 months
Incidence of ≥Grade 3 treatment related, non-hematologic toxicity
41 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Collaborators

Genentech, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2008

Primary Completion (ACTUAL)

October 1, 2009

Study Completion (ACTUAL)

January 1, 2011

Study Registration Dates

First Submitted

January 29, 2008

First Submitted That Met QC Criteria

February 11, 2008

First Posted (ESTIMATE)

February 12, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

July 16, 2013

Last Update Submitted That Met QC Criteria

July 10, 2013

Last Verified

July 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00003768

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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