Phase I/II Trial of Radiosurgery Plus Bevacizumab in Patients With Recurrent/Progressive Glioblastoma
Inclusion Criteria
Inclusion
- 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
contraception
- For females of child-bearing potential, negative serum pregnancy test within 14 days
prior to entry
Exclusion
- 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
entry
- 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