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Phase II Trial of Low-Dose Whole Brain Radiotherapy With Concurrent Temozolomide and Adjuvant Temozolomide in Patients With Newly-Diagnosed Glioblastoma Multiforme (GCC 1224)

This study is currently recruiting participants.
Verified July 2017 by Department of Radiation Oncology, University of Maryland
Sponsor:
ClinicalTrials.gov Identifier:
NCT01822275
First Posted: April 2, 2013
Last Update Posted: August 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Department of Radiation Oncology, University of Maryland
  Purpose

In the current proposed trial the role of the low-dose WBRT (0.15 Gy) would be to safely treat the microscopic distant GBM cells outside of the high dose RT region and sensitize the gross tumor, while the focal radiation dose (1.85 Gy) to the gross tumor will bring the total tumor dose of 2 Gy per fraction which is the standard of care.

Radiotherapy (RT) has been integral in the treatment of GBM since the 1970s when Walker et al. showed that post-operative whole brain radiotherapy (WBRT) offered significant improvements in median survival time, and even more so when given with concomitant BCNU chemotherapy. Ensuing dose escalation studies found the optimal dose to be 60 Gy. Patients could not tolerate escalation to higher doses than 60 Gy with WBRT due to unacceptable toxicity. Even with WBRT of 60 Gy, a huge volume of healthy brain tissue was unnecessarily treated with high-dose radiation; recurrences with WBRT remained overwhelmingly local. Hochberg and Pruitt (1980) found that after WBRT only 3% of recurrences were outside 2 cm of the margins of the primary tumor. With the rise of the CT scan in the 1980s and the MRI in the 1990s, along with subsequent improvements in three-dimensional conformal radiation, partial brain RT (PBRT) became practical since tumor margins could be visualized and irradiated more accurately. - Subsequently, WBRT was shown to provide no survival benefit over PBRT at the same dosage; - thus, the latter took over as the standard of care.


Condition Intervention Phase
Histologically Proven Diagnosis of Glioblastoma or Gliosarcoma (WHO Grade IV) Drug: Chemotherapy with Temodar. Radiation: Radiation therapy Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Low-Dose Whole Brain Radiotherapy With Concurrent Temozolomide and Adjuvant Temozolomide in Patients With Newly-Diagnosed Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by Department of Radiation Oncology, University of Maryland:

Primary Outcome Measures:
  • Efficacy of low-dose whole brain RT (WBRT)in patients with GBM [ Time Frame: 2017 ]
    To determine the safety and efficacy of low-dose whole brain RT (WBRT) when given concurrently to the standard TMZ and focal partial brain RT (efficacy will be measured by decreased distant disease recurrence rate).


Secondary Outcome Measures:
  • Radiographic (CT-MRI) response assesment and treatment failure patterns of patients with GBM [ Time Frame: 2017 ]
    To determine the radiographic response with the combination therapy. To determine the treatment failure patterns after the combination therapy.


Estimated Enrollment: 47
Study Start Date: May 2013
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Low Dose WBRT
Once the patient has had surgery, patients will receive 6 weeks of radiation therapy with concurrent chemotherapy on protcol. This will be followed by either 6 or a maximum of 12 cycles of adjuvent chemotherapy with Temodar.
Drug: Chemotherapy with Temodar.
Once the patient has had surgery, patients will receive 6 weeks of radiation therapy with concurrent chemotherapy on protcol. This will be followed by a maximum of 12 cycles of adjuvent chemotherapy with Temodar.
Radiation: Radiation therapy

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 3.1.1 Histologically proven diagnosis of glioblastoma or gliosarcoma (WHO grade IV).

3.1.2 Infratentorial and multi-focal tumors are eligible. 3.1.3 History and physical with neurological examination, steroid documentation, height, and weight within 14 days of registration.

3.1.4 A diagnstic contrast-enhanced MRI of the brain must be performed preoperatively and postoperatively prior to the initiation of radiotherapy. The postoperative scan must be performed within 28 days prior to registration. (contrast enhanced Brain CT is allowed if MRI is contraindicated) 3.1.5 Karnofsky performance status ≥ 70 or ECOG performance status ≤ 2. 3.1.6 Age ≥ 18. 3.1.7 CBC with differential obtained within 14 days prior to registration, with adequate bone marrow function defined as follows:

  • Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3.
  • Platelets ≥ 100,000 cells/mm3.
  • Hemoglobin ≥ 10.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥10.0 g/dl is acceptable).

3.1.8 Adequate renal function within 14 days prior to registration, as defined below:

  • BUN ≤ 30 mg/dl.
  • Creatinine ≤ 1.7 mg/dl. 3.1.9 Adequate hepatic function within 14 days prior to registration, as defined below:
  • Bilirubin ≤ 2.0 mg/dl.
  • ALT/AST ≤ 3 x upper limit of normal (ULN). 3.1.10 Systolic blood pressure ≤ 160 mg Hg or diastolic pressure ≤ 90 mg Hg within 14 days prior to registration.

3.1.11 Prothrombin time/international normalized ratio (PT INR) < 1.4 for patients not on warfarin confirmed by testing within 14 days prior to registration. Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria:

  • No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices).
  • In-range INR (between 2.5 and 3.5) on a stable dose of warfarin-based oral anticoagulant; or on a stable dose of low molecular weight heparin; or INR between 1.5 and 2 if a Greenfield filter is in place.

3.1.12 Patient must provide study specific informed consent prior to study entry.

3.1.13 For women of child-bearing potential, negative serum pregnancy test within 14 days prior to registration.

3.1.14 Women o f childbearing potential and male participants must practice adequate contraception.

Exclusion Criteria:

  • 3.2.1 Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years. For example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible.

3.2.2 Metastases beyond the cranial vault. 3.2.3 Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment is not permitted.

3.2.4 Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in significant overlap of radiation fields.

3.2.5 Severe, active co-morbidity, defined as follows:

  • Unstable angina and/or congestive heart failure within the last 6 months.
  • Transmural myocardial infarction within the last 6 months.
  • New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to registration.
  • History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months.
  • Serious and inadequately controlled cardiac arrhythmia.
  • Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease.
  • Evidence of bleeding diathesis or coagulopathy.
  • Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess, major surgical procedure or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for tumor resection or follow-on craniotomies to manage complications of brain tumor management such as hemorrhage or infection.
  • Bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol.
  • Acquired immune deficiency syndrome (AIDS) based upon current CDC definition; Note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol are significantly immunosuppressive.
  • Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity.
  • Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.
  • Cognitive impairment that precludes a patient from acting as his or her own agent to provide informed consent.

3.2.6 Women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the chemotherapeutic treatment involved in this study is significantly teratogenic.

3.2.7 Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to study treatment.

3.2.8 Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study.

3.2.9 Inability to undergo MRI (e.g., due to safety reasons, such as presence of a pacemaker).

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01822275


Contacts
Contact: Caroline Poff, RN 410-369-5264 caroline.poff@umm.edu

Locations
United States, Maryland
Ummc Msgcc Recruiting
Baltimore, Maryland, United States, 21201
Contact: Caroline Poff, RN    410-369-5264    caroline.poff@umm.edu   
Sponsors and Collaborators
University of Maryland
Investigators
Principal Investigator: Young Kwok, MD University of Maryland
  More Information

Responsible Party: Department of Radiation Oncology, Associate Professor, University of Maryland
ClinicalTrials.gov Identifier: NCT01822275     History of Changes
Other Study ID Numbers: HP-00053043
First Submitted: March 22, 2013
First Posted: April 2, 2013
Last Update Posted: August 1, 2017
Last Verified: July 2017

Keywords provided by Department of Radiation Oncology, University of Maryland:
GBM

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