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Phase I/II Trial of Radiosurgery Plus Bevacizumab in Patients With Recurrent/Progressive Glioblastoma

Phase 1/Phase 2
18 Years
Open (Enrolling)
Glioblastoma, Gliosarcoma, Brain Tumor

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Trial Information

Phase I/II Trial of Radiosurgery Plus Bevacizumab in Patients With Recurrent/Progressive Glioblastoma


I. To determine the overall survival of patients with recurrent GBM treated with
bevacizumab, irinotecan and radiosurgery


I. To evaluate the toxicities of the combination of bevacizumab, irinotecan and

II. To evaluate the progression-free survival of patients treated with bevacizumab,
irinotecan and radiosurgery.


Patients receive bevacizumab IV over 30 minutes on days 1 and 15. Patients also receive
irinotecan hydrochloride IV on days 1 and 15 beginning in course 2. Courses repeat every 28
days in the absence of disease progression or unacceptable toxicity.

Patients undergo radiosurgery 10-14 days after beginning bevacizumab.

After completion of study treatment, patients are followed for 18 months.

Inclusion Criteria


- Histologically proven diagnosis of glioblastoma or gliosarcoma (WHO grade IV) at
primary or subsequent resection

- Radiographic evidence of tumor progression as defined by a contrast enhanced MRI at
least 3 months after the completion of radiation therapy

- Unifocal enhancing disease; the enhancing focus must be =< 3 cm in maximum diameter

- History/physical examination within 14 days prior to registration

- The patient must have recovered from the effects of prior therapy before study entry

- The patient must not have received chemotherapy within the following time frames:
Non-cytotoxic agents: 2 weeks, cytotoxic agents: 3 weeks, nitrosoureas: 6 weeks

- Must be able to undergo MRI imaging

- Documentation of steroid doses within 14 days prior to registration

- Karnofsky performance status > 60

- Absolute neutrophil count (ANC) >= 1,500 cells/mm^3

- Platelets >= 100,000 cells/mm^3

- Hemoglobin >= 10.0 g/dl (Note: The use of transfusion or other intervention to
achieve Hgb >= 10.0 g/dl is acceptable)

- BUN =< 30 mg/dl within 14 days prior to study entry

- Creatinine =< 1.7 mg/dl within 14 days prior to study entry

- Urine protein screened by urine analysis for urine protein creatinine (UPC) ratio;
for UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be
< 1000 mg

- Bilirubin =< 2.0 mg/dl within 14 days prior to study entry

- ALT/AST =< 3 x normal range within 14 days prior to study entry

- Electrocardiogram without evidence of acute cardiac ischemia within 14 days prior
study entry

- Prothrombin time/international normalized ratio (PT INR) < 1.4 for patients not on
warfarin confirmed by testing within 14 days prior to study entry

- 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 and 3) on a stable dose of oral anticoagulant or on a stable
dose of low molecular weight heparin

- Patients must provide study specific informed consent prior to study entry

- Women of childbearing potential and male participants must practice adequate

- For females of child-bearing potential, negative serum pregnancy test within 14 days
prior to entry


- 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)

- More than one focus of enhancement

- Involvement of the brainstem (defined as the midbrain or lower)

- Prior use of chemotherapy wafers or any other intratumoral or intracavitary treatment
are not permitted; prior radiosurgery is not permitted

- Prior treatment with intravenous bevacizumab

- Unstable angina and/or congestive heart failure within the last 6 months

- Transmural myocardial infarction within the last 6 months

- Evidence of recent myocardial infarction or ischemia by the findings of S-T
elevations of >= 2 mm using the analysis of an EKG performed within 14 days of entry

- 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

- Uncontrolled hypertension

- 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, intra-abdominal abscess major surgical
procedure, open biopsy, or significant traumatic injury within 28 days prior to
registration, with the exception of the craniotomy for tumor resection

- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy at the time of entry

- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
note, however, that laboratory tests for liver function and 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

- 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

- Pregnancy or women of childbearing potential and men who are sexually active and not
willing/able to use medically acceptable forms of contraception

- Pregnant or lactating women, due to possible adverse effects on the developing fetus
or infant due to study drug

- Patients treated on any other therapeutic clinical trials within 30 days prior to
study entry or during participation in the study

- Growth factors are not permitted to induce elevations in neutrophil count for the
purposes of: 1) administration of temozolomide on the scheduled dosing interval; 2)
allowing treatment with temozolomide at a higher dose; or 3) avoiding interruption of
the treatment during concomitant radiotherapy

- No other investigational drugs will be allowed during this study

- Surgical procedures for tumor debulking, other types of chemotherapy, and
immunotherapy or biologic therapy must not be used

- Additional stereotactic boost radiotherapy is not allowed

Type of Study:


Study Design:

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

Outcome Measure:

Overall survival of patients with recurrent GBM treated with bevacizumab, irinotecan and radiosurgery

Outcome Time Frame:

Patients are followed for 18 months.

Safety Issue:


Principal Investigator

Michael Vogelbaum, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

February 2010

Completion Date:

Related Keywords:

  • Glioblastoma
  • Gliosarcoma
  • Brain Tumor
  • adult giant cell glioblastoma
  • adult gliosarcoma
  • recurrent adult brain tumor
  • Brain Neoplasms
  • Glioblastoma
  • Gliosarcoma



Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer CenterCleveland, Ohio  44195