Radiosurgery Plus Bevacizumab in Glioblastoma

NCT01086345 | Terminated Early Phase 1 DMC

• 2 other identifiers: CASE4309NCI-2010-00309
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma; Gliosarcoma; Brain Tumor

Keywords

adult giant cell glioblastoma; adult gliosarcoma; recurrent adult brain tumor

Outcome Measures

Primary Outcomes (1)

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

  Patients are followed for 18 months.

Secondary Outcomes (2)

• 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.

Study Arms (1)

Arm I

EXPERIMENTAL

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; Biological: bevacizumab; Drug: irinotecan hydrochloride

Interventions

radiosurgery RADIATION

Patients undergo radiosurgery 10-14 days after beginning bevacizumab.

Also known as: Radiation Surgery

Arm I

bevacizumab BIOLOGICAL

Given IV

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, anti-VEGF rhuMAb, Avastin, recombinant humanized anti-VEGF monoclonal antibody, rhuMAb VEGF

Arm I

irinotecan hydrochloride DRUG

Given IV

Also known as: Campto, Camptosar, camptothecin-11, CPT-11, irinotecan, U-101440E

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Brain Neoplasms

Interventions

Radiosurgery; Bevacizumab; Irinotecan

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Michael Vogelbaum, MD

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2010
• First Posted: March 15, 2010
• Study Start: February 1, 2010
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: July 3, 2018

Record last verified: 2018-06

Locations

US (1)