A Dose Per Fraction Escalation Trial of Hypofractionated IMRT With Temozolomide for Newly Diagnosed Glioblastoma

March 23, 2017 updated by: University of Colorado, Denver

A Phase I Dose Per Fraction Escalation Study of Hypofractionated Intensity-Modulated Radiation Therapy (Hypo-IMRT) Combining With Temozolomide (TMZ) Chemotherapy for Patients With Newly Diagnosed Glioblastoma Multiforme (GBM)

The purpose of the study is to find out the highest dose per fraction of hypofractionated Intensity-Modulated Radiation Therapy (Hypo-IMRT) that can be safely given with temozolomide chemotherapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Hypo-IMRT is given in fewer treatments than conventional radiation therapy. This will be a dose per fraction escalation study. A dose per fraction escalation study means that successive groups of patients will receive higher doses per fraction of radiation while keeping the total dose of radiation the same (60 Gy, Gy is a radiation unit). The radiation dose per fraction will be increased and the numbers of radiation treatments will be decreased until a fraction dose is reached at which there are unacceptable side effects compared with possible benefit. Which group subjects are assigned to will depend on what stage the study has reached at the time the subject decide to participate.

This research is being done because with current standard radiation therapy (A total dose of 60 Gy given 2 Gy a day over 6 weeks) the outcome is very poor. New and more effective radiation therapy methods are desperately needed for patients with GBM.

In this study, radiation therapy is given together with chemotherapy of Temozolomide.

This study is also designed to monitor the level of some of the known cytokines (specific proteins in the blood) before and after radiation, and in meantime to screen unknown proteins in patients' blood before and after radiation therapy. Hopefully, this will provide some clues for future study of monitoring radiation damage, and possibly new therapeutic approach for patients with GBM.

Study Type

Interventional

Enrollment (Actual)

37

Phase

  • Phase 1

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
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado 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:

  • Histopathologically confirmed WHO grade IV astrocytoma (GBM), tumor can be supra- or infra-tentorial in location but not located in the brain stem.
  • Solitary or multifocal tumor.
  • Tumor can be biopsied or resected, either totally or sub-totally.
  • A pre-radiation therapy brain MRI is mandatory.
  • Surgical cavity or surgical cavity + T1 enhancing residual tumor ≤ 6 cm in the largest diameter on the pre-radiation therapy MRI. In the case of multifocal tumor, the combined largest diameter of T1 enhancing tumor + surgical cavity ≤ 6 cm.
  • Placement of bis-chloronitrosourea (BCNU) wafers at the time of surgery is allowed.
  • Age > 18 years at time of registration.
  • Estimated survival of at least 3 months.
  • Zubrod Performance Scale of 0-2 (Karnofsky performance scale ≥ 60).
  • Hgb > 9 gm; absolute neutrophil count (ANC) > 1500/ul; platelets > 100,000; Creatinine < 1.5 times the upper limit of laboratory normal value; Bilirubin < 2 times the upper limit of laboratory normal value; serum glutamate pyruvate transaminase (SGPT) or serum glutamate oxaloacetate transaminase (SGOT) < 3 times the upper limit of laboratory normal value.
  • Patients must sign study-specific informed consent form prior to registration.
  • Men and women and members of all ethnic groups are eligible for this trial.
  • Radiation therapy and chemotherapy must start within 8 weeks of tumor resection or biopsy

Exclusion Criteria:

  • Patients with contraindications for MRI scanning.
  • Prior temozolomide chemotherapy.
  • Prior brain irradiation.
  • Evidence of severe or uncontrolled psychiatric or systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease) that would interfere with study protocol as judged by the investigator.
  • Acquired Immune Deficiency (HIV (+)/AIDS)
  • Patients being treated on any other clinical protocols within 30 days prior to study entry or during participation in the study.
  • Pregnant women or breast feeding women. Women of childbearing potential must practice medically approved contraceptive precautions. Men should be counseled and agreeable to follow acceptable birth control methods.
  • Active connective tissue disorders, such as active lupus or scleroderma.
  • Concurrent active malignancy at other sites.
  • Frequent vomiting of medical condition which could interfere with oral medication intake (e.g. partial bowel obstruction).

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: Glioblastoma Multiforme Patients
Hypofractionated Intensity-Modulated Radiation Therapy (Hypo-IMRT) Combining with Temozolomide (TMZ) Chemotherapy
Radiation: Hypofractionated Intensity-Modulated Radiation Therapy
All patients will receive one fraction of radiation therapy a day, 5 days a week, Monday through Friday. Radiation fraction size and number of fractions depend on dose fraction level the patient is assigned to.
Drug: Temozolomide
Temozolomide will be administered orally, once a day starting on the first day of radiation, for 28 consecutive days during radiation, and after radiation for those patients completing radiation in less than 28 days.
Other Names:
  • Temodar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To identify the maximum dose per fraction of IMRT a patient can tolerate while keeping the total radiation dose at 60 Gy, provided concurrently with daily oral temozolomide chemotherapy
Time Frame: Up to 60 days
To determine the frequency of patients developing >= grade 3 acute and delayed toxicities attributable to radiotherapy. Acute radiotherapy toxicities are defined as those toxicities which occur during and within 30 days from the completion of radiotherapy and delayed toxicity are those developed at least 30 days after the last dose of radiation.
Up to 60 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: Until disease progression
To monitor the level of some of the known and unknown cytokines or proteins before and after Hypo-IMRT and correlate it with the incidence of acute and late neurotoxicity. Quality of life assessment before and after treatment.
Until disease progression

Collaborators and Investigators

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

Sponsor

University of Colorado, Denver

Investigators

  • Principal Investigator: Douglas Ney, M.D, University of Colorado, Denver

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)

November 1, 2005

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

July 1, 2016

Study Registration Dates

First Submitted

November 13, 2008

First Submitted That Met QC Criteria

November 14, 2008

First Posted (Estimate)

November 17, 2008

Study Record Updates

Last Update Posted (Actual)

March 27, 2017

Last Update Submitted That Met QC Criteria

March 23, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 05-0562.cc

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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.

Clinical Trials on Glioblastoma Multiforme

Clinical Trials on Hypofractionated Intensity-Modulated Radiation Therapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Slovenia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe