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A Pilot Phase II Trial of Hypofractionated Intensity-Modulated Radiation Therapy (Hypo-IMRT) Combining With Temozolomide (TMZ) and Bevacizumab for Patients With Newly Diagnosed Glioblastoma Multiforme (GBM)

Phase 2
18 Years
Open (Enrolling)
Glioblastoma Multiforme

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Trial Information

A Pilot Phase II Trial of Hypofractionated Intensity-Modulated Radiation Therapy (Hypo-IMRT) Combining With Temozolomide (TMZ) and Bevacizumab for Patients With Newly Diagnosed Glioblastoma Multiforme (GBM)

This is a pilot phase II trial of the combination of concurrent hypofractionated IMRT (60
Gy/2 weeks), temozolomide and bevacizumab followed by 6 cycles of adjuvant bevacizumab and
temozolomide in patients with grade IV malignant gliomas (glioblastoma and gliosarcoma). The
study will have survival and toxicity endpoints.

Inclusion Criteria:

- Histologically confirmed diagnosis of WHO grade IV primary malignant glioma (GBM or

- Age ≥ 18 years at the time of study registration

- Karnofsky Performance Scale ≥ 60%

- Absolute Neutrophil Count (ANC) ≥ 1,500 cells/mm3, hemoglobin ≥ 9.0 g/dl, platelets ≥
100,000 cells/ mm3

- Serum creatinine ≤ 1.5 mg/dl, serum glutamate oxaloacetate transaminase (SGOT) and
bilirubin ≤ 1.5 times upper limit of normal

- Signed informed consent approved by the Institutional Review Board

- Craniotomy or intracranial biopsy site must be adequately healed, free of drainage or
cellulitis, and the underlying cranioplasty must appear intact at the time of study
entry. Study treatment should be initiated > 28 days following the last surgical
procedure (including open biopsy, surgical resection, wound revision, or any other
major surgery involving entry into a body cavity)

Exclusion Criteria:

- Life expectancy of less than 12 weeks

- Prior treatment, including radiation therapy or chemotherapy, for GBM with the
exception of surgery (Gliadel Wafers are allowed at the time of surgery)

- Active malignancy, with the exception of superficial basal cell and/or superficial
squamous (skin) cell, or carcinoma in situ of the cervix

- Active infection requiring IV antibiotics

- Pregnant or breast feeding

- International normalized ratio (INR) > 1.5 and activated partial thromboplastin time
(aPTT) > 1.5 × the upper limit of normal (ULN) (except for subjects receiving
anticoagulation therapy) in the absence of therapeutic intent to anticoagulate the
subject. Therapeutic anticoagulation is permitted

- Evidence of ≥ Common Toxicity Criteria for Adverse Effects (CTCAE) v.3 grade 2 CNS
hemorrhage (CNS hemorrhage when medical intervention indicated), but grade 1 CNS
hemorrhage (asymptomatic radiographic findings on the baseline brain CT or MRI only)
is allowed. Punctate hemorrhage or the presence of hemosiderin is not considered a
Grade 1 event for the purpose of this study. )

- Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg
and/or diastolic blood pressure > 100 mmHg)

- Prior history of hypertensive crisis or hypertensive encephalopathy

- Current New York Heart Association (NYHA) Grade II or greater congestive heart

- History of myocardial infarction or unstable angina within 6 months prior to

- History of stroke or transient ischemic attack within 6 months prior to enrollment

- Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or
recent peripheral arterial thrombosis) within 6 months prior to enrollment

- History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month
prior to enrollment

- Evidence of bleeding diathesis or significant coagulopathy (in the absence of
therapeutic anticoagulation)

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to enrollment or anticipation of need for major surgical procedure during the
course of the study

- Core needle biopsy or other minor surgical procedure, excluding placement of a
vascular access device, within 7 days prior to enrollment

- History of abdominal fistula or gastrointestinal perforation within 6 months prior to

- Serious, non-healing wound, active ulcer, or untreated bone fracture

- Proteinuria as demonstrated by a Urine protein-creatinine ratios (UPC) ratio ≥ 1.0
at screening (Appendix A).

- Known hypersensitivity to any component of bevacizumab

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

6-month progression-free survival

Outcome Description:

To use 6-month progression-free survival to assess the efficacy of the combination of hypofractionated IMRT delivering 60 Gy over 2 weeks with concurrent bevacizumab and temozolomide followed by 6 cycles of adjuvant bevacizumab and temozolomide.

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Changhu Chen, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Colorado, Denver


United States: Institutional Review Board

Study ID:



Start Date:

August 2010

Completion Date:

December 2014

Related Keywords:

  • Glioblastoma Multiforme
  • Glioblastoma



University of Colorado Denver, University of Colorado Cancer CenterAurora, Colorado  80045