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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT00792012
First received: November 13, 2008
Last updated: June 27, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Glioblastoma Multiforme
Radiation: Hypofractionated Intensity-Modulated Radiation Therapy
Drug: Temozolomide
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

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 [ Time Frame: Up to 60 days ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Until deases progression ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 27
Study Start Date: November 2005
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Temodar

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 effect compared with possible benefit. Which group you are in will depend on what stage the study has reached at the time you 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 the patients like you 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 us with some clues for future study of monitoring radiation damage, and possibly new therapeutic approach for patients like you with GBM.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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. Patients with contraindications for MRI scanning are ineligible for this study.
  • 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 cannot be treated on any other clinical protocols within 30 days prior to study entry or during participation in the study.
  • 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.
  • No active connective tissue disorders, such as active lupus or scleroderma.
  • Radiation therapy and chemotherapy must start within 8 weeks of tumor resection or biopsy

Exclusion Criteria:

  • 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)
  • 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.
  • concurrent active malignancy at other sites.
  • frequent vomiting of medical condition which could interfere with oral medication intake (e.g. partial bowel obstruction).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00792012

Locations
United States, Colorado
University of Colorado Cancer Center
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Douglas Ney, M.D University of Colorado, Denver
  More Information

No publications provided by University of Colorado, Denver

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT00792012     History of Changes
Other Study ID Numbers: 05-0562.cc
Study First Received: November 13, 2008
Last Updated: June 27, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Colorado, Denver:
Glioblastoma Multiforme

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014