Biologically-based Target Volumes to Treat Newly Diagnosed Glioblastoma

September 4, 2020 updated by: John M. Buatti

Phase II Study of High Dose Radiotherapy and Concurrent Temozolomide Using Biologically-based Target Volume Definition in Patients With Newly Diagnosed Glioblastoma

This clinical trial increases radiation to areas of the brain considered to be at risk for cancer. The at-risk areas are identified by a biological MRI scan. The study will look at side effects of the radiation and overall survival.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

This study evaluates if increasing radiation dose to at-risk areas impacts overall survival without causing a decrease in quality of life or an increase in radiation side effects.

Standard radiation dose for glioblastoma (GBM) is 60 Gray in 30 fractions, with patients receiving 1 fraction per day, Monday through Friday.

This trial will use a total of 75 Gray in 30 fractions, with participants receiving 1 fraction per day, Monday through Friday. Participants will still receive the standard chemotherapy (temozolomide) at the standard dose (75 mg/m2, once daily, 7 days a week).

This study also uses a different imaging technique to identify the tumor target and the tissues at risk. Normal imaging techniques will be used to define the standard target volume and will receive the standard radiation dose (60 Gray). A special MRI sequence will identify at risk areas based on diffusion and perfusion abnormalities. This area will receive the higher radiation dose (75 Gray).

Participants will also be asked to complete quality of life questionnaires and neurocognitive evaluations at specific time points. This is to identify any side effects from the higher radiation dose. Preliminary work done at University of Michigan suggests a lack of side effects from the higher dose of radiation.

Study Type

Interventional

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
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Department of Radiation Oncology

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:

  • Ability to understand and willingness to provide informed consent
  • Newly diagnosed, histologically-confirmed supratentorial WHO grade IV gliomas including glioblastoma (all variants) and gliosarcoma.
  • Patients must be 18 years of age or older.≥
  • Karnofsky performance status ≥ 70
  • Minimal life expectancy of 12 weeks.
  • Maximal contiguous volume of tumor based on high b-value diffusion MRI and perfusion MRI < 1/3 volume of brain
  • Patients must be treated within 6 weeks of most recent resection

Within 21 days of radiation fraction 1, the following blood test parameters must be met:

  • Hemoglobin ≥ 10 g/dL (transfusion is acceptable)
  • absolute neutrophils ≥ 1500/mm3
  • platelet count ≥ 100,000/mm3
  • total bilirubin ≤ 2 x upper limit of normal (ULN) (unless elevated bilirubin is related to Gilbert syndrome)
  • ALT and AST ≤ 5 x ULN
  • serum creatinine ≤ 2.0 mg/dL

Exclusion Criteria:

  • Recurrent glioma, or tumor involving the brainstem or cerebellum. Prior low-grade glioma without prior RT, now with malignant progression are eligible.
  • Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment is not permitted. Prior chemotherapy for a different cancer is allowable if interval since last treatment cycle completion is >3 years.
  • Evidence of CSF dissemination (positive CSF cytology for malignancy or MRI findings consistent with CSF dissemination).
  • Multifocal disease (>1 lobe of involvement) of discontiguous, contrast enhancing disease as seen on conventional MRI
  • Evidence of severe concurrent disease requiring treatment
  • Known active malignancy as determined by treating medical and radiation oncologist
  • Patients unable to undergo MRI exams
  • Patients treated with previous cranial or head/neck radiotherapy leading to significant radiation field overlap.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring inpatient hospitalization or delay treatment, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or compromise subject safety.
  • Pregnant women are excluded from this study because ionizing radiation is a known teratogen, and temozolomide is a Class D agent with the potential for teratogenic or abortifacient effects.
  • Nursing mothers declining to discontinue breastfeeding are excluded because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with temozolomide.
  • Patients with reproductive potential declining to use an effective contraceptive method during treatment are excluded from this study.

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: Radiation Therapy
External beam radiation therapy delivered to target volume.
Radiation: External beam radiation therapy
Radiotherapy to 75 Gy Radiation delivered 1 fraction / day, Monday through Friday, for a total of 30 fractions
Other Names:
  • radiation
  • radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 12 months after completing radiation therapy
Estimate 12-month overall survival of GBM patients treated with 75 Gray of radiation based on advanced MRI planning, with concurrent temozolomide.
12 months after completing radiation therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival (PFS)
Time Frame: Every 2 months, for up to 60 months after completing radiation therapy, until progression or death from any cause
Estimate progression-free survival (PFS) in GBM patients treated with 75 Gray of radiation based on advanced MRI planning, with concurrent temozolomide.
Every 2 months, for up to 60 months after completing radiation therapy, until progression or death from any cause
Identifying tissue at risk of recurrence
Time Frame: 12 months after completing radiation therapy
Assess the ability of pre-treatment and mid-treatment advanced MRI to determine areas at high risk of recurrence
12 months after completing radiation therapy
Distinguish progression from pseudoprogression
Time Frame: 12 months after completing radiation therapy
Assess the ability of post-treatment advanced MRI to distinguish progression from pseudoprogression
12 months after completing radiation therapy
Adverse events related to treatment
Time Frame: Weekly during radiation therapy, every 2 months post-radiation therapy for 7 months, then 13 & 19 months post-radiation
Provide descriptive data regarding health-related quality of life (QOL), symptoms and neurocognitive function
Weekly during radiation therapy, every 2 months post-radiation therapy for 7 months, then 13 & 19 months post-radiation

Collaborators and Investigators

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

Sponsor

John M. Buatti

Collaborators

Holden Comprehensive Cancer Center

Investigators

  • Principal Investigator: John M. Buatti, MD, University of Iowa

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.

General Publications

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)

May 15, 2019

Primary Completion (Anticipated)

December 31, 2024

Study Completion (Anticipated)

December 31, 2026

Study Registration Dates

First Submitted

April 12, 2018

First Submitted That Met QC Criteria

April 20, 2018

First Posted (Actual)

April 23, 2018

Study Record Updates

Last Update Posted (Actual)

September 9, 2020

Last Update Submitted That Met QC Criteria

September 4, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201801819

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Deidentified Individual participant data will be shared with a signed usage agreement. Additionally, a contract will be required between University of Iowa and the receiving institution.

IPD Sharing Time Frame

Upon request

IPD Sharing Access Criteria

Email study contacts with request

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)
  • Analytic Code

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

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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