Bevacizumab, Temozolomide and Hypofractionated Radiotherapy for Patients With Newly Diagnosed Malignant Glioma

January 10, 2018 updated by: Memorial Sloan Kettering Cancer Center

A Phase II Study of Bevacizumab, Temozolomide and Hypofractionated Radiotherapy for Patients With Newly Diagnosed Malignant Glioma

The purpose of this study is to test the safety of a new plan for treating glioblastoma. The usual first treatment for glioblastoma is to give focused radiation over 6 weeks in combination with a chemotherapy called temozolomide. In this study the radiation will be given over 2 weeks in combination with temozolomide and another drug, bevacizumab, will also be given. Our idea is that this treatment plan may attack both the tumor and the blood vessels feeding the tumor more effectively. This study will look at what effects, good or bad, this approach has on the patient and the tumor.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

40

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
    • New Jersey
      • Basking Ridge, New Jersey, United States
        • Memoral Sloan Kettering Cancer Center
    • New York
      • Commack, New York, United States, 11725
        • Memorial Sloan-Kettering Cancer Center at Commack
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center

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:

  • Pathologic diagnosis of glioblastoma or grade IV glioma.
  • Tumor volume should be less than 60 cc (approximately 5cm maximum diameter).
  • Age > or = to 18
  • KPS ≥70
  • Granulocyte count >1.5 X 10 9/L
  • Platelet count >99 X 10 9/L
  • SGOT < 2.5X upper limit of normal (ULN)
  • Serum creatinine < 2X ULN
  • Bilirubin < 2X ULN
  • All patients must sign written informed consent

Exclusion Criteria:

  • Any prior chemotherapy, radiotherapy and biologic therapy for glioma.
  • Any prior experimental therapy for glioma.
  • Multicentric glioma
  • Other concurrent active malignancy (with the exception of cervical carcinoma in situ or basal cell ca of the skin).
  • Serious medical or psychiatric illness that would in the opinion of the investigator interfere with the prescribed treatment.
  • Pregnant or breast feeding women.
  • Refusal to use effective contraception
  • Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg)
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure
  • History of myocardial infarction or unstable angina within 12 months prior to Day 1
  • History of stroke or transient ischemic attack
  • Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
  • History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of treatment 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 Day 1
  • History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
  • Serious, non-healing wound, active ulcer, or untreated bone fracture
  • Proteinuria as demonstrated by a UPC ratio ≥ 1.0 at screening
  • Known hypersensitivity to any component of bevacizumab

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: RT, with temozolomide and bevacizumab
This treatment regimen is novel in that it delivers the initial course of RT over 2 weeks instead of 6 weeks; also, the addition of bevacizumab during and after RT is a new approach.
Other: radiotherapy (RT) in combination with temozolomide and bevacizumab

Bevacizumab10 mg/kg IV once every two weeks on days 1 and 15 of every cycle (Cycle defined as 28 days). Temozolomide 75mg/m2 daily beginning on day 1 through completion of radiotherapy. Hypofractionated dose painting IMRT will start on day 1 and will be delivered on a Monday, Wednesday, Friday schedule for a total of 6 fractions.

Post RT therapy: Bevacizumab 10mg/kg IV every two weeks. Temozolomide 150-200mg/m2 daily for 5 consecutive days will be given on 28 day cycles.

Follow up: CBC weekly, comprehensive panel and urinalysis monthly, blood pressure every other week. Neurological/physical examination monthly. Gd-enhanced MRI with perfusion every 2 cycles. Neurocognitive testing (approximately 4months post RT, 1 year after diagnosis and then annually in long term survivors). Blood sample for correlative studies monthly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events
Time Frame: through study completion, an average of 1 year
Safety assessments and toxicity grading will follow CTCAE Version 4 Grade
through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Time Frame
Progression Free Survival
Time Frame: through study completion, an average of 1 year
through study completion, an average of 1 year
Neurocognitive Outcome
Time Frame: through study completion, an average of 1 year
through study completion, an average of 1 year

Collaborators and Investigators

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

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

Genentech, Inc.
National Institutes of Health (NIH)

Investigators

  • Principal Investigator: Antonio Omuro, MD, Memorial Sloan Kettering Cancer Center

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 (Actual)

October 28, 2008

Primary Completion (Actual)

March 23, 2017

Study Completion (Actual)

March 23, 2017

Study Registration Dates

First Submitted

October 29, 2008

First Submitted That Met QC Criteria

October 29, 2008

First Posted (Estimate)

October 31, 2008

Study Record Updates

Last Update Posted (Actual)

February 6, 2018

Last Update Submitted That Met QC Criteria

January 10, 2018

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-126

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

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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