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

• ClinicalTrials.gov Identifier: NCT00792012
• Recruitment Status: Completed
• First Posted: November 17, 2008
• Last Update Posted: March 27, 2017
• Sponsor: University of Colorado, Denver
• Information provided by (Responsible Party): University of Colorado, Denver

Tracking Information

• First Submitted Date: November 13, 2008
• First Posted Date: November 17, 2008
• Last Update Posted Date: March 27, 2017
• Actual Study Start Date: November 2005
• Actual Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 24, 2013)

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.

• Original Primary Outcome Measures (submitted: November 14, 2008): 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
• Change History: Complete list of historical versions of study NCT00792012 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: December 3, 2015)

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.

• Original Secondary Outcome Measures (submitted: November 14, 2008): Progression-free survival. To monitor the level of some of the known and unknown cytokines or proteins before and after Hypo-IMRT & correlate it with the incidence of acute and late neurotoxicity. Quality of life assessment before & after treatment.
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)
• 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Glioblastoma Multiforme

Intervention

• 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 Name: Temodar

Study Arms

Experimental: Glioblastoma Multiforme Patients

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

Interventions:

• Radiation: Hypofractionated Intensity-Modulated Radiation Therapy
• Drug: Temozolomide

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 6, 2016): 37
• Original Estimated Enrollment (submitted: November 14, 2008): 27
• Actual Study Completion Date: July 2016
• Actual Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00792012
• Other Study ID Numbers: 05-0562.cc
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: University of Colorado, Denver
• Study Sponsor: University of Colorado, Denver
• Collaborators: Not Provided

Investigators

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

• PRS Account: University of Colorado, Denver
• Verification Date: March 2017