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

Primary Purpose

Glioblastoma Multiforme

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Hypofractionated Intensity-Modulated Radiation Therapy

Temozolomide

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring Glioblastoma Multiforme

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

University of Colorado Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Glioblastoma Multiforme Patients

Arm Description

Hypofractionated Intensity-Modulated Radiation Therapy (Hypo-IMRT) Combining with Temozolomide (TMZ) Chemotherapy

Outcomes

Primary Outcome Measures

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

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.

Secondary Outcome Measures

Progression-free survival

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.

Full Information

NCT ID

NCT00792012

First Posted

November 13, 2008

Last Updated

March 23, 2017

Sponsor

University of Colorado, Denver

1. Study Identification

Unique Protocol Identification Number

NCT00792012

Brief Title

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

Official Title

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)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Completed

Study Start Date

November 2005 (Actual)

Primary Completion Date

July 2016 (Actual)

Study Completion Date

July 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Colorado, Denver

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma Multiforme

Keywords

Glioblastoma Multiforme

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

37 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Glioblastoma Multiforme Patients

Arm Type

Experimental

Arm Description

Hypofractionated Intensity-Modulated Radiation Therapy (Hypo-IMRT) Combining with Temozolomide (TMZ) Chemotherapy

Intervention Type

Radiation

Intervention Name(s)

Hypofractionated Intensity-Modulated Radiation Therapy

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Temozolomide

Other Intervention Name(s)

Temodar

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Up to 60 days

Secondary Outcome Measure Information:

Title

Progression-free survival

Description

Time Frame

Until disease progression

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Douglas Ney, M.D

Organizational Affiliation

University of Colorado, Denver

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Colorado Cancer Center

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

22483738

Citation

Reddy K, Damek D, Gaspar LE, Ney D, Waziri A, Lillehei K, Stuhr K, Kavanagh BD, Chen C. Phase II trial of hypofractionated IMRT with temozolomide for patients with newly diagnosed glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 2012 Nov 1;84(3):655-60. doi: 10.1016/j.ijrobp.2012.01.035. Epub 2012 Apr 5.

Results Reference

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

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