Radiosurgery Plus Bevacizumab in Glioblastoma

Sponsor

Case Comprehensive Cancer Center (Other)

Overall Status

Terminated

CT.gov ID

NCT01086345

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Radiosurgery can send x-rays directly to the tumor and cause less damage to normal tissue. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of glioblastoma by blocking blood flow to the tumor. Drugs used in chemotherapy such as irinotecan hydrochloride work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiosurgery together with bevacizumab and irinotecan hydrochloride may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving radiosurgery together with bevacizumab and irinotecan hydrochloride works in treating patients with recurrent glioblastoma.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma Gliosarcoma Brain Tumor	Radiation: radiosurgery Biological: bevacizumab Drug: irinotecan hydrochloride	Early Phase 1

Detailed Description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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

Study Design

Study Type:

Interventional

Actual Enrollment :

9 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2010

Actual Primary Completion Date :

Dec 1, 2014

Actual Study Completion Date :

Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I 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.	Radiation: radiosurgery Patients undergo radiosurgery 10-14 days after beginning bevacizumab. Other Names: Radiation Surgery Biological: bevacizumab Given IV Other Names: anti-VEGF humanized monoclonal antibody anti-VEGF monoclonal antibody anti-VEGF rhuMAb Avastin recombinant humanized anti-VEGF monoclonal antibody rhuMAb VEGF Drug: irinotecan hydrochloride Given IV Other Names: Campto Camptosar camptothecin-11 CPT-11 irinotecan U-101440E

Arm

Intervention/Treatment

Experimental: Arm I

Radiation: radiosurgery

Patients undergo radiosurgery 10-14 days after beginning bevacizumab.

Other Names:

Radiation Surgery

Biological: bevacizumab

Given IV

Other Names:

anti-VEGF humanized monoclonal antibody

anti-VEGF monoclonal antibody

anti-VEGF rhuMAb

Avastin

recombinant humanized anti-VEGF monoclonal antibody

rhuMAb VEGF

Drug: irinotecan hydrochloride

Given IV

Other Names:

Campto

Camptosar

camptothecin-11

CPT-11

irinotecan

U-101440E

Outcome Measures

Primary Outcome Measures

Overall survival of patients with recurrent GBM treated with bevacizumab, irinotecan and radiosurgery [Patients are followed for 18 months.]

Secondary Outcome Measures

Treatment-related toxicity [Courses repeat every 28 days in the absence of unacceptable toxicity.]
Progression-free survival, defined as the interval from randomization to progression or death, whichever occurs first [Patients are followed for 18 months.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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