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


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

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Trial Information

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


PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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

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

OUTLINE:

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


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

Type of Study:

Interventional

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:

No

Principal Investigator

Michael Vogelbaum, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

CASE4309

NCT ID:

NCT01086345

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

Name

Location

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